Is CD151 p.Pro181Ser (c.541C>T) pathogenic?

CD151 p.Pro181Ser (c.541C>T) is classified Uncertain significance in CD151 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-02-01). AlphaMissense: likely pathogenic (0.9879); Very rare (popmax 8.47e-05%, nfe); Associated with RAPH BLOOD GROUP SYSTEM.

What condition is associated with CD151 p.Pro181Ser (c.541C>T)?

CD151 p.Pro181Ser (c.541C>T) is associated with RAPH BLOOD GROUP SYSTEM, epidermolysis bullosa simplex 7, with nephropathy and deafness (ClinVar).

How common is CD151 p.Pro181Ser (c.541C>T) in the general population?

CD151 p.Pro181Ser (c.541C>T) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about CD151 p.Pro181Ser (c.541C>T)?

AlphaMissense predicts likely pathogenic (score 0.9879) — an in-silico prediction, not a clinical call.

CD151 p.Pro181Ser

c.541C>T · rs1846822053 · VCV1943752

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely pathogenic

0.9879 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

RAPH BLOOD GROUP SYSTEM

Computational evidence

Protein change
AlphaMissense	0.9879	likely pathogenic · top 5% in CD151
REVEL	0.84	moderately pathogenic-leaning
SaProt	LLR -14.72	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 2,119 bp · p 0.3 · regional, not allelic
Overall
CADD	24.8	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 8.47e-05% European (non-Finnish) · 1/1,179,952 alleles

Overall 6.85e-05% 1/1,460,818 alleles · very rare

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: CD151
Protein: p.Pro181Ser
Coding: c.541C>T
MANE Select: NM_004357
dbSNP: rs1846822053
Type: single nucleotide variant
Location: chr11:837544 (GRCh38)
Gene constraint: LOEUF 0.816 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 88.02

Full CD151 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

RAPH BLOOD GROUP SYSTEM — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: epidermolysis bullosa simplex 7, with nephropathy and deafness

Similar variants

CD151 p.Lys7Ter Pathogenic ★★ same condition
CD151 c.352-11C>G Uncertain significance ★★ same condition
CD151 c.702+4A>G Uncertain significance ★★ same condition
CD151 c.702+5G>C Uncertain significance ★★ same condition
CD151 p.Ala145Thr Uncertain significance ★★ ⚠ same condition
CD151 p.Ala81Thr Uncertain significance ★★ ⚠ same condition
CD151 p.Arg133Cys Uncertain significance ★★ ⚠ same condition
CD151 p.Arg165Gln Uncertain significance ★★ ⚠ 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/cd151-p-pro181ser (accessed [today's date]).

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