Is CD6 p.Ala271Thr (c.811G>A) pathogenic?

CD6 p.Ala271Thr (c.811G>A) is classified Benign in CD6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-12-03). AlphaMissense: likely benign (0.0746); Common (popmax 18.9%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with CD6-related disorder.

What condition is associated with CD6 p.Ala271Thr (c.811G>A)?

CD6 p.Ala271Thr (c.811G>A) is associated with CD6-related disorder (ClinVar).

What do computational predictors say about CD6 p.Ala271Thr (c.811G>A)?

AlphaMissense predicts likely benign (score 0.0746) — an in-silico prediction, not a clinical call.

CD6 p.Ala271Thr

Q: How common is CD6 p.Ala271Thr (c.811G>A) in the general population?

CD6 p.Ala271Thr (c.811G>A) is common (popmax 18.9%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.811G>A · rs12360861 · VCV3060441

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0746 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 18.9%, nfe) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

CD6-related disorder

Computational evidence

Protein change
AlphaMissense	0.0746	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -3.20	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 -6.9	GERP -4.4
Regional constraint	o/e 0.86	unconstrained · MANE · 47 kb · p 2.2e-05 · regional, not allelic
Overall
CADD	0.03	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 18.9% European (non-Finnish) · 222,488/1,178,560 alleles

Filtering AF 18.8% ClinGen BA1/BS1 input FAF95, joint · FAF99 18.8%

Overall 16.3% 262,335/1,610,542 alleles · common

Ancestry group	Frequency	1 in
Amishnot grpmax-eligible	34.3%	3
European (non-Finnish)grpmax	18.9%	5
Middle Eastern	17.8%	6
Remaining individualsnot grpmax-eligible	15%	7
Ashkenazi Jewishnot grpmax-eligible	13.3%	8
Finnishnot grpmax-eligible	13.2%	8
Admixed American	11.1%	9
South Asian	6.53%	15
African / African-American	5.76%	17
East Asian	0.0357%	2,802

Amish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ala271Thr
Coding: c.811G>A
MANE Select: NM_006725
dbSNP: rs12360861
Type: single nucleotide variant
Location: chr11:61009601 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.14 · 1 PDB
Residue 271: a UniProt-annotated variant site (in); a β-strand; the srcr 3 domain

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.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-ala271thr (accessed [today's date]).

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