Is CD8B p.Ala60Thr (c.178G>A) pathogenic?

CD8B p.Ala60Thr (c.178G>A) is classified Uncertain significance in CD8B (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-28). AlphaMissense: likely benign (0.0987); Ultra-rare (popmax 0.0329%, mid).

How common is CD8B p.Ala60Thr (c.178G>A) in the general population?

CD8B p.Ala60Thr (c.178G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about CD8B p.Ala60Thr (c.178G>A)?

AlphaMissense predicts likely benign (score 0.0987) — an in-silico prediction, not a clinical call.

CD8B p.Ala60Thr

c.178G>A · rs1248329743 · VCV2591344

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0987 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0987	likely benign
REVEL	0.033	moderately benign-leaning
SaProt	LLR -5.22	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.9
Regional constraint	o/e 0.72	unconstrained · MANE · 20 kb · p 4.9e-06 · regional, not allelic
Overall
CADD	12.88	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0329% Middle Eastern · 2/6,078 alleles

Filtering AF 0.0058% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00241%

Overall 0.000805% 13/1,613,910 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,039
Remaining individualsnot grpmax-eligible	0.0032%	31,234
Admixed American	0.00167%	59,996
European (non-Finnish)	0.000678%	147,486

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: CD8B
Protein: p.Ala60Thr
Coding: c.178G>A
MANE Select: NM_004931
dbSNP: rs1248329743
Type: single nucleotide variant
Location: chr2:86858282 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 82.03
Residue 60: the ig-like v-type domain; a disulfide bond

Full CD8B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD8B p.Ala190Thr Uncertain significance ★ ⚠ same type
CD8B p.Arg156Trp Uncertain significance ★ ⚠ same type
CD8B p.Arg201Gln Uncertain significance ★ ⚠ same type
CD8B p.Arg203Cys Uncertain significance ★ ⚠ same type
CD8B p.Arg51His Uncertain significance ★ ⚠ same type
CD8B p.Arg98Gln Uncertain significance ★ ⚠ same type
CD8B p.Arg98Leu Uncertain significance ★ ⚠ same type
CD8B p.Gln23Lys Uncertain significance ★ ⚠ same type

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/cd8b-p-ala60thr (accessed [today's date]).

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