Is CD151 p.Ala81Thr (c.241G>A) pathogenic?

CD151 p.Ala81Thr (c.241G>A) is classified Uncertain significance in CD151 (ClinVar, Multiple submitters, 5 submitters; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.7706); Ultra-rare (popmax 0.0609%, nfe); Associated with epidermolysis bullosa simplex 7, with nephropathy and deafness.

What condition is associated with CD151 p.Ala81Thr (c.241G>A)?

CD151 p.Ala81Thr (c.241G>A) is associated with epidermolysis bullosa simplex 7, with nephropathy and deafness (ClinVar).

How common is CD151 p.Ala81Thr (c.241G>A) in the general population?

CD151 p.Ala81Thr (c.241G>A) is ultra-rare (popmax 0.0609%, nfe) (gnomAD).

What do computational predictors say about CD151 p.Ala81Thr (c.241G>A)?

AlphaMissense predicts likely pathogenic (score 0.7706) — an in-silico prediction, not a clinical call.

CD151 p.Ala81Thr

Q: How is Nephrotic syndrome-epidermolysis bullosa-sensorineural deafness syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.241G>A · rs141569440 · VCV1428000

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely pathogenic

0.7706 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0609%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

epidermolysis bullosa simplex 7, with nephropathy and deafness

Computational evidence

Protein change
AlphaMissense	0.7706	likely pathogenic
REVEL	0.705	pathogenic-leaning
SaProt	LLR -10.19	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 11	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 2,119 bp · p 0.3 · regional, not allelic
Overall
CADD	30.0	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 0.0609% European (non-Finnish) · 719/1,179,698 alleles

Filtering AF 0.0572% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0558%

Overall 0.0464% 748/1,611,340 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0609%	1,641
Remaining individualsnot grpmax-eligible	0.016%	6,246
Finnishnot grpmax-eligible	0.0146%	6,852
African / African-American	0.00933%	10,721
East Asian	0.00446%	22,439
Admixed American	0.00167%	59,986

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.Ala81Thr
Coding: c.241G>A
MANE Select: NM_004357
dbSNP: rs141569440
Type: single nucleotide variant
Location: chr11:836407 (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

epidermolysis bullosa simplex 7, with nephropathy and deafness — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Nephrotic syndrome-epidermolysis bullosa-sensorineural deafness syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adolescent

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.Arg133Cys Uncertain significance ★★ ⚠ same condition
CD151 p.Arg165Gln Uncertain significance ★★ ⚠ same condition
CD151 p.Arg171Cys 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-ala81thr (accessed [today's date]).

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