Is CD6 p.Pro433= (c.1299C>T) pathogenic?

CD6 p.Pro433= (c.1299C>T) is classified Likely benign in CD6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-03-05). Ultra-rare (popmax 0.0179%, eas); Associated with CD6-related disorder.

What condition is associated with CD6 p.Pro433= (c.1299C>T)?

CD6 p.Pro433= (c.1299C>T) is associated with CD6-related disorder (ClinVar).

How common is CD6 p.Pro433= (c.1299C>T) in the general population?

CD6 p.Pro433= (c.1299C>T) is ultra-rare (popmax 0.0179%, eas) (gnomAD).

CD6 p.Pro433=

c.1299C>T · rs567700137 · VCV3057359

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0179%, eas)

Conditions

CD6-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.059	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -16	GERP -4.3
Overall
CADD	0.468	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0179% East Asian · 8/44,700 alleles

Filtering AF 0.00886% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00643%

Overall 0.00484% 78/1,610,666 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0179%	5,587
Remaining individualsnot grpmax-eligible	0.0128%	7,791
European (non-Finnish)	0.00518%	19,318
Admixed American	0.00168%	59,396

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.Pro433=
Coding: c.1299C>T
MANE Select: NM_006725
dbSNP: rs567700137
Type: single nucleotide variant
Location: chr11:61013926 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.14 · 1 PDB

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.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-pro433 (accessed [today's date]).

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