Is CD6 p.Ser130Cys (c.388A>T) pathogenic?

CD6 p.Ser130Cys (c.388A>T) is classified Uncertain significance in CD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-23). AlphaMissense: likely pathogenic (0.5838); Very rare (popmax 0.00281%, nfe).

How common is CD6 p.Ser130Cys (c.388A>T) in the general population?

CD6 p.Ser130Cys (c.388A>T) is very rare (popmax 0.00281%, nfe) (gnomAD).

What do computational predictors say about CD6 p.Ser130Cys (c.388A>T)?

AlphaMissense predicts likely pathogenic (score 0.5838) — an in-silico prediction, not a clinical call.

CD6 p.Ser130Cys

c.388A>T · VCV3264860

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5838 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00281%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5838	likely pathogenic
REVEL	0.144	moderately benign-leaning
SaProt	LLR -12.23	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.6	GERP -4
Regional constraint	o/e 0.86	unconstrained · MANE · 47 kb · p 2.2e-05 · regional, not allelic
Overall
CADD	14.63	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 0.00281% European (non-Finnish) · 31/1,104,184 alleles

Filtering AF 0.00201% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00175%

Overall 0.00215% 31/1,444,462 alleles · very rare exomes 27/1,292,332 · genomes 4/152,130 · joint denominator

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.Ser130Cys
Coding: c.388A>T
MANE Select: NM_006725
Type: single nucleotide variant
Location: chr11:61007829 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.14 · 1 PDB
Residue 130: the srcr 1 domain; a β-strand

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-ser130cys (accessed [today's date]).

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