Is CD6 p.Ala257= (c.771G>C) pathogenic?

CD6 p.Ala257= (c.771G>C) is classified Benign in CD6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-11-01). Common (popmax 27.5%, afr) — too common for a highly-penetrant pathogenic allele; Associated with CD6-related disorder.

What condition is associated with CD6 p.Ala257= (c.771G>C)?

CD6 p.Ala257= (c.771G>C) is associated with CD6-related disorder (ClinVar).

CD6 p.Ala257=

Q: How common is CD6 p.Ala257= (c.771G>C) in the general population?

CD6 p.Ala257= (c.771G>C) is common (popmax 27.5%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.771G>C · rs79848107 · VCV3059695

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 27.5%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

CD6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.026	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.69	GERP -4.4, phastCons 1
Overall
CADD	9.554	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 27.5% African / African-American · 20,137/73,194 alleles

Filtering AF 27.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 27.1%

Overall 13.6% 210,378/1,541,770 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	27.5%	4
Amishnot grpmax-eligible	22.4%	4
Middle Eastern	19.2%	5
South Asian	15.7%	6
Ashkenazi Jewishnot grpmax-eligible	14.2%	7
Remaining individualsnot grpmax-eligible	14%	7
European (non-Finnish)	13.3%	8
Admixed American	10%	10
Finnishnot grpmax-eligible	8.01%	12
East Asian	6.82%	15

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.Ala257=
Coding: c.771G>C
MANE Select: NM_006725
dbSNP: rs79848107
Type: single nucleotide variant
Location: chr11:61008835 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.14 · 1 PDB
Residue 257: a disulfide bond; a UniProt-annotated variant site (in); the srcr 2 domain; a β-strand

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

Disease context

CD6-related disorder

Similar variants

CD6 p.Ala257Val Benign same residue
CD6 c.49+8C>T Benign same condition
CD6 p.Ala271Thr Benign same condition
CD6 p.Ala605= Benign same condition
CD6 p.Arg225Trp Benign same condition
CD6 p.Gly606Ser Benign same condition
CD6 p.Pro433= Likely benign same condition
CD6 p.Pro454= Likely benign same condition

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-ala257 (accessed [today's date]).

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