Is CD6 p.Leu15Pro (c.44T>C) pathogenic?

CD6 p.Leu15Pro (c.44T>C) is classified Uncertain significance in CD6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.2339); Very rare (popmax 0.004%, afr).

How common is CD6 p.Leu15Pro (c.44T>C) in the general population?

CD6 p.Leu15Pro (c.44T>C) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about CD6 p.Leu15Pro (c.44T>C)?

AlphaMissense predicts likely benign (score 0.2339) — an in-silico prediction, not a clinical call.

CD6 p.Leu15Pro

c.44T>C · VCV4222983

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2339 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2339	likely benign
REVEL	0.185	benign-leaning
SaProt	LLR -7.91	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 3.9	GERP 1.8, phastCons 0.68
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

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.004% African / African-American · 3/74,948 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000806% 13/1,613,816 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.004%	24,983
European (non-Finnish)	0.000847%	117,997

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.Leu15Pro
Coding: c.44T>C
MANE Select: NM_006725
Type: single nucleotide variant
Location: chr11:60971909 (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

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-leu15pro (accessed [today's date]).

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