Is CD6 p.Gly166Arg (c.496G>C) pathogenic?

CD6 p.Gly166Arg (c.496G>C) is classified Uncertain significance in CD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-11-22). AlphaMissense: likely pathogenic (0.6971); Ultra-rare (popmax 0.0101%, amr).

How common is CD6 p.Gly166Arg (c.496G>C) in the general population?

CD6 p.Gly166Arg (c.496G>C) is ultra-rare (popmax 0.0101%, amr) (gnomAD).

What do computational predictors say about CD6 p.Gly166Arg (c.496G>C)?

AlphaMissense predicts likely pathogenic (score 0.6971) — an in-silico prediction, not a clinical call.

CD6 p.Gly166Arg

c.496G>C · rs762653723 · VCV3140640

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6971 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, amr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.6971	likely pathogenic
REVEL	0.399	indeterminate
SaProt	LLR -12.67	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 2.2, phastCons 1
Regional constraint	o/e 0.86	unconstrained · MANE · 47 kb · p 2.2e-05 · regional, not allelic
Overall
CADD	24.7	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

Grpmax group 0.0101% Admixed American · 6/59,290 alleles

Filtering AF 0.00433% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00298%

Overall 0.00118% 19/1,605,440 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0101%	9,882
Remaining individualsnot grpmax-eligible	0.00805%	12,418
African / African-American	0.00134%	74,794
European (non-Finnish)	0.000595%	168,069

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.Gly166Arg
Coding: c.496G>C
MANE Select: NM_006725
dbSNP: rs762653723
Type: single nucleotide variant
Location: chr11:61008560 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.14 · 1 PDB
Residue 166: a β-strand; the srcr 2 domain

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-gly166arg (accessed [today's date]).

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