Is CD6 p.Thr217Met (c.650C>T) pathogenic?

CD6 p.Thr217Met (c.650C>T) is classified Benign in CD6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-22). AlphaMissense: likely benign (0.1435); Common (popmax 31.8%, mid) — too common for a highly-penetrant pathogenic allele; Associated with CD6-related disorder.

What condition is associated with CD6 p.Thr217Met (c.650C>T)?

CD6 p.Thr217Met (c.650C>T) is associated with CD6-related disorder (ClinVar).

What do computational predictors say about CD6 p.Thr217Met (c.650C>T)?

AlphaMissense predicts likely benign (score 0.1435) — an in-silico prediction, not a clinical call.

CD6 p.Thr217Met

Q: How common is CD6 p.Thr217Met (c.650C>T) in the general population?

CD6 p.Thr217Met (c.650C>T) is common (popmax 31.8%, mid) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.650C>T · rs11230562 · VCV3056065

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1435 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 31.8%, mid) — 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	0.1435	likely benign
REVEL	0.046	moderately benign-leaning
SaProt	LLR -7.57	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 -0.12	GERP -4.4
Regional constraint	o/e 0.86	unconstrained · MANE · 47 kb · p 2.2e-05 · regional, not allelic
Overall
CADD	22.6	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 31.8% Middle Eastern · 1,926/6,048 alleles

Filtering AF 30.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 30.2%

Overall 20.6% 331,098/1,606,434 alleles · common

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	42.8%	2
Middle Easterngrpmax	31.8%	3
Amishnot grpmax-eligible	26.2%	4
European (non-Finnish)	23.3%	4
Remaining individualsnot grpmax-eligible	21%	5
Finnishnot grpmax-eligible	17.2%	6
Admixed American	12.7%	8
South Asian	7.73%	13
African / African-American	4.09%	24
East Asian	2.35%	43

Ashkenazi Jewish 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.Thr217Met
Coding: c.650C>T
MANE Select: NM_006725
dbSNP: rs11230562
Type: single nucleotide variant
Location: chr11:61008714 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.14 · 1 PDB
Residue 217: a disulfide bond; a UniProt-annotated variant site (in); the srcr 2 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.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-thr217met (accessed [today's date]).

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