Is CD8A p.Tyr124Asn (c.370T>A) pathogenic?

CD8A p.Tyr124Asn (c.370T>A) is classified Uncertain significance in CD8A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-02-24). AlphaMissense: ambiguous (0.5299); Very rare (popmax 0.00333%, amr); Associated with susceptibility to respiratory infections associated with CD8alpha chain mutation.

How common is CD8A p.Tyr124Asn (c.370T>A) in the general population?

CD8A p.Tyr124Asn (c.370T>A) is very rare (popmax 0.00333%, amr) (gnomAD).

What do computational predictors say about CD8A p.Tyr124Asn (c.370T>A)?

AlphaMissense predicts ambiguous (score 0.5299) — an in-silico prediction, not a clinical call.

CD8A p.Tyr124Asn

Q: What condition is associated with CD8A p.Tyr124Asn (c.370T>A)?

CD8A p.Tyr124Asn (c.370T>A) is associated with susceptibility to respiratory infections associated with CD8alpha chain mutation (ClinVar).

Q: How is Susceptibility to respiratory infections associated with CD8alpha chain mutation inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.370T>A · rs904075671 · VCV1057353

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5299 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00333%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

susceptibility to respiratory infections associated with CD8alpha chain mutation

Computational evidence

Protein change
AlphaMissense	0.5299	ambiguous
REVEL	0.204	benign-leaning
SaProt	LLR -6.98	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	Δ0.20	donor loss, 2 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP -0.47	GERP -3
Regional constraint	o/e 1.13	unconstrained · MANE · 4,902 bp · p 0.024 · regional, not allelic
Overall
CADD	15.51	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00333% Admixed American · 2/60,006 alleles

Filtering AF 0.00114% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000971%

Overall 0.00167% 27/1,613,920 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00469%	21,318
Admixed Americangrpmax	0.00333%	30,003
European (non-Finnish)	0.00178%	56,190
Remaining individualsnot grpmax-eligible	0.0016%	62,484

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: CD8A
Protein: p.Tyr124Asn
Coding: c.370T>A
MANE Select: NM_001768
dbSNP: rs904075671
Type: single nucleotide variant
Location: chr2:86790361 (GRCh38)
Gene constraint: LOEUF 1.496 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.03 · 8 PDB
Residue 124: a β-strand; the ig-like v-type domain

Full CD8A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

susceptibility to respiratory infections associated with CD8alpha chain mutation — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Susceptibility to respiratory infections associated with CD8alpha chain mutation (Orphanet):

Inheritance: Autosomal recessive
Onset: Infancy, Neonatal
Prevalence: <1 / 1 000 000 (Europe)

Similar variants

CD8A p.Tyr124Phe Uncertain significance ★ ⚠ same residue
CD8A p.Tyr124= Likely benign ★ same residue
CD8A c.403+4C>G Uncertain significance ★★ same condition
CD8A c.626-2A>T Uncertain significance ★★ same condition
CD8A p.Arg165Leu Uncertain significance ★★ ⚠ same condition
CD8A p.Arg165Pro Uncertain significance ★★ ⚠ same condition
CD8A p.His127Tyr Uncertain significance ★★ ⚠ same condition
CD8A p.His208Leu Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/cd8a-p-tyr124asn (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown