Is CD8A p.Phe128Val (c.382T>G) pathogenic?

CD8A p.Phe128Val (c.382T>G) is classified Uncertain significance in CD8A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-20). AlphaMissense: ambiguous (0.3499); Absent from gnomAD v4.1.

How common is CD8A p.Phe128Val (c.382T>G) in the general population?

CD8A p.Phe128Val (c.382T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD8A p.Phe128Val (c.382T>G)?

AlphaMissense predicts ambiguous (score 0.3499) — an in-silico prediction, not a clinical call.

CD8A p.Phe128Val

c.382T>G · VCV3264891

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3499 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.3499	ambiguous
REVEL	0.208	benign-leaning
SaProt	LLR -7.17	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.3	GERP 0.42, phastCons 0.98
Regional constraint	o/e 1.13	unconstrained · MANE · 4,902 bp · p 0.024 · regional, not allelic
Overall
CADD	15.81	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CD8A
Protein: p.Phe128Val
Coding: c.382T>G
MANE Select: NM_001768
Type: single nucleotide variant
Location: chr2:86790349 (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 128: an α-helix; the ig-like v-type domain

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

Similar variants

CD8A p.Phe128= Likely benign ★ same residue
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

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-phe128val (accessed [today's date]).

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