Is CD6 p.Pro315Thr (c.943C>A) pathogenic?

CD6 p.Pro315Thr (c.943C>A) is classified Uncertain significance in CD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-26). AlphaMissense: ambiguous (0.3665); Absent from gnomAD v4.1.

How common is CD6 p.Pro315Thr (c.943C>A) in the general population?

CD6 p.Pro315Thr (c.943C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CD6 p.Pro315Thr (c.943C>A)?

AlphaMissense predicts ambiguous (score 0.3665) — an in-silico prediction, not a clinical call.

CD6 p.Pro315Thr

c.943C>A · rs2539308209 · VCV2303593

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3665 · 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	0.3665	ambiguous
REVEL	0.117	moderately benign-leaning
SaProt	LLR -7.64	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 2.9	GERP 2.2, phastCons 0.86
Regional constraint	o/e 0.86	unconstrained · MANE · 47 kb · p 2.2e-05 · regional, not allelic
Overall
CADD	21.8	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: CD6
Protein: p.Pro315Thr
Coding: c.943C>A
MANE Select: NM_006725
dbSNP: rs2539308209
Type: single nucleotide variant
Location: chr11:61009733 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.14 · 1 PDB
Residue 315: a disulfide bond; the srcr 3 domain; an α-helix

Full CD6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD6 p.Ala151Val Uncertain significance ★ ⚠ same type
CD6 p.Ala160Val Uncertain significance ★ ⚠ same type
CD6 p.Ala22Asp Uncertain significance ★ ⚠ same type
CD6 p.Ala235Thr Uncertain significance ★ ⚠ same type
CD6 p.Ala311Glu Uncertain significance ★ ⚠ same type
CD6 p.Ala431Asp Uncertain significance ★ ⚠ same type
CD6 p.Ala78Thr Uncertain significance ★ ⚠ same type
CD6 p.Arg220Ser 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/cd6-p-pro315thr (accessed [today's date]).

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