Is CD8A p.Ala80= (c.240G>C) pathogenic?

CD8A p.Ala80= (c.240G>C) is classified Likely benign in CD8A (ClinVar, Single submitter, 1 submitter; last evaluated 2022-04-01). Very rare (popmax 0.000169%, nfe).

How common is CD8A p.Ala80= (c.240G>C) in the general population?

CD8A p.Ala80= (c.240G>C) is very rare (popmax 0.000169%, nfe) (gnomAD).

CD8A p.Ala80=

c.240G>C · rs755909430 · VCV2651103

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.000169%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.4	GERP -3.1
Overall
CADD	5.199	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000169% European (non-Finnish) · 2/1,180,032 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.00131% 2/152,198 alleles · very rare

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.Ala80=
Coding: c.240G>C
MANE Select: NM_001768
dbSNP: rs755909430
Type: single nucleotide variant
Location: chr2:86790491 (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 80: the ig-like v-type domain; a disulfide bond

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

Similar variants

CD8A c.403+4C>G Uncertain significance ★★ same type
CD8A c.626-2A>T Uncertain significance ★★ same type
CD8A p.Arg165Leu Uncertain significance ★★ ⚠ same type
CD8A p.Arg165Pro Uncertain significance ★★ ⚠ same type
CD8A p.His127Tyr Uncertain significance ★★ ⚠ same type
CD8A p.His208Leu Uncertain significance ★★ ⚠ same type
CD8A p.Leu10Arg Uncertain significance ★★ ⚠ same type
CD8A p.Pro130Arg 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/cd8a-p-ala80 (accessed [today's date]).

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