Is CD6 p.Ala431Asp (c.1292C>A) pathogenic?

CD6 p.Ala431Asp (c.1292C>A) is classified Uncertain significance in CD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: ambiguous (0.4903); Very rare (popmax 0.00247%, nfe).

How common is CD6 p.Ala431Asp (c.1292C>A) in the general population?

CD6 p.Ala431Asp (c.1292C>A) is very rare (popmax 0.00247%, nfe) (gnomAD).

What do computational predictors say about CD6 p.Ala431Asp (c.1292C>A)?

AlphaMissense predicts ambiguous (score 0.4903) — an in-silico prediction, not a clinical call.

CD6 p.Ala431Asp

c.1292C>A · VCV3998303

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4903 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00247%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4903	ambiguous
REVEL	0.219	benign-leaning
SaProt	LLR -6.64	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 5.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 47 kb · p 2.2e-05 · regional, not allelic
Overall
CADD	27.6	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

Grpmax group 0.00247% European (non-Finnish) · 29/1,175,092 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0015%

Overall 0.00187% 30/1,604,472 alleles · very rare exomes 28/1,452,184 · genomes 2/152,288 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00247%	40,520
Remaining individualsnot grpmax-eligible	0.00161%	62,082

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: CD6
Protein: p.Ala431Asp
Coding: c.1292C>A
MANE Select: NM_006725
Type: single nucleotide variant
Location: chr11:61013919 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.14 · 1 PDB

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.Ala78Thr Uncertain significance ★ ⚠ same type
CD6 p.Arg220Ser Uncertain significance ★ ⚠ same type
CD6 p.Arg266His 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-ala431asp (accessed [today's date]).

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