Is CD6 p.Ser612Pro (c.1834T>C) pathogenic?

CD6 p.Ser612Pro (c.1834T>C) is classified Likely benign in CD6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-07-02). AlphaMissense: likely benign (0.0753); Rare (popmax 0.712%, afr); Associated with CD6-related disorder.

What condition is associated with CD6 p.Ser612Pro (c.1834T>C)?

CD6 p.Ser612Pro (c.1834T>C) is associated with CD6-related disorder (ClinVar).

How common is CD6 p.Ser612Pro (c.1834T>C) in the general population?

CD6 p.Ser612Pro (c.1834T>C) is rare (popmax 0.712%, afr) (gnomAD).

What do computational predictors say about CD6 p.Ser612Pro (c.1834T>C)?

AlphaMissense predicts likely benign (score 0.0753) — an in-silico prediction, not a clinical call.

CD6 p.Ser612Pro

c.1834T>C · rs140201536 · VCV3038452

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0753 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.712%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CD6-related disorder

Computational evidence

Protein change
AlphaMissense	0.0753	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -5.08	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.67	GERP -3.1
Regional constraint	o/e 0.86	unconstrained · MANE · 47 kb · p 2.2e-05 · regional, not allelic
Overall
CADD	2.575	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 0.712% African / African-American · 534/74,966 alleles

Filtering AF 0.662% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.643%

Overall 0.0365% 588/1,610,724 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.712%	140
Admixed American	0.0467%	2,143
Remaining individualsnot grpmax-eligible	0.0385%	2,597
Middle Eastern	0.0209%	4,784
European (non-Finnish)	8.48e-05%	1,179,647

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.Ser612Pro
Coding: c.1834T>C
MANE Select: NM_006725
dbSNP: rs140201536
Type: single nucleotide variant
Location: chr11:61018010 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.14 · 1 PDB
Residue 612: the 'disordered' region

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

Disease context

CD6-related disorder

Similar variants

CD6 c.49+8C>T Benign same condition
CD6 p.Ala257= Benign same condition
CD6 p.Ala257Val 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

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-ser612pro (accessed [today's date]).

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