Is CD8B p.Gly127Val (c.380G>T) pathogenic?

CD8B p.Gly127Val (c.380G>T) is classified Uncertain significance in CD8B (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely pathogenic (0.8794); Absent from gnomAD v4.1.

How common is CD8B p.Gly127Val (c.380G>T) in the general population?

CD8B p.Gly127Val (c.380G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD8B p.Gly127Val (c.380G>T)?

AlphaMissense predicts likely pathogenic (score 0.8794) — an in-silico prediction, not a clinical call.

CD8B p.Gly127Val

c.380G>T · rs2466679432 · VCV2251046

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8794 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8794	likely pathogenic · top 4% in CD8B
REVEL	0.735	pathogenic-leaning
SaProt	LLR -16.59	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	phastCons 1
Regional constraint	o/e 0.72	unconstrained · MANE · 20 kb · p 4.9e-06 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

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: CD8B
Protein: p.Gly127Val
Coding: c.380G>T
MANE Select: NM_004931
dbSNP: rs2466679432
Type: single nucleotide variant
Location: chr2:86858080 (GRCh38)
Gene constraint: LOEUF 0.764 · pLI 0.42 (gnomAD)
Structure: AlphaFold pLDDT 82.03
Residue 127: the ig-like v-type domain

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

Similar variants

CD8B p.Gly127Arg Uncertain significance ★ ⚠ same residue
CD8B p.Ala190Thr Uncertain significance ★ ⚠ same type
CD8B p.Ala60Thr 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

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-gly127val (accessed [today's date]).

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