Is CD8A p.Ala171fs (c.509dup) pathogenic?

CD8A p.Ala171fs (c.509dup) is classified Uncertain significance in CD8A (ClinVar, Single submitter, 1 submitter; last evaluated 2020-02-11). Very rare (popmax 0.000179%, nfe); Associated with susceptibility to respiratory infections associated with CD8alpha chain mutation.

How common is CD8A p.Ala171fs (c.509dup) in the general population?

CD8A p.Ala171fs (c.509dup) is very rare (popmax 0.000179%, nfe) (gnomAD).

CD8A p.Ala171fs

Q: What condition is associated with CD8A p.Ala171fs (c.509dup)?

CD8A p.Ala171fs (c.509dup) 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.509dup · rs1673182671 · VCV1009961

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.000179%, nfe)

Conditions

susceptibility to respiratory infections associated with CD8alpha chain mutation

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 3 of 6
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 0.031	GERP -0.56
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	tandem	(CCGCCC)n simple repeat · ambiguous alignment · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000179% European (non-Finnish) · 2/1,118,832 alleles

Filtering AF 3e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000271% 4/1,478,570 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.00469%	21,333
European (non-Finnish)grpmax	0.000179%	559,416

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.Ala171fs
Coding: c.509dup
MANE Select: NM_001768
dbSNP: rs1673182671
Type: Duplication
Location: chr2:86789644 (GRCh38)
Gene constraint: LOEUF 1.496 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.03 · 8 PDB

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.Ala171Thr Uncertain significance ★ ⚠ same residue
CD8A c.656+18_656+19dup Benign/Likely benign ★★ same condition
CD8A c.41_50-20dup Likely benign ★ same condition
CD8A c.514+11dup Likely benign ★ same condition
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

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-ala171fs (accessed [today's date]).

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