Is CD151 p.Tyr115Cys (c.344A>G) pathogenic?

CD151 p.Tyr115Cys (c.344A>G) is classified Uncertain significance in CD151 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-05). AlphaMissense: ambiguous (0.4346); Very rare (popmax 0.00134%, afr); Associated with epidermolysis bullosa simplex 7, with nephropathy and deafness.

What condition is associated with CD151 p.Tyr115Cys (c.344A>G)?

CD151 p.Tyr115Cys (c.344A>G) is associated with epidermolysis bullosa simplex 7, with nephropathy and deafness (ClinVar).

How common is CD151 p.Tyr115Cys (c.344A>G) in the general population?

CD151 p.Tyr115Cys (c.344A>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CD151 p.Tyr115Cys (c.344A>G)?

AlphaMissense predicts ambiguous (score 0.4346) — an in-silico prediction, not a clinical call.

CD151 p.Tyr115Cys

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.344A>G · VCV3574093

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4346 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

epidermolysis bullosa simplex 7, with nephropathy and deafness

Computational evidence

Protein change
AlphaMissense	0.4346	ambiguous
REVEL	0.657	pathogenic-leaning
SaProt	LLR -10.76	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 2,119 bp · p 0.3 · regional, not allelic
Overall
CADD	24.3	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 0.00134% African / African-American · 1/74,858 alleles

Filtering AF 0.000247% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000159%

Overall 0.000496% 8/1,612,302 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,858
European (non-Finnish)	0.000593%	168,537

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.Tyr115Cys
Coding: c.344A>G
MANE Select: NM_004357
Type: single nucleotide variant
Location: chr11:836836 (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.Tyr115His Uncertain significance ★ ⚠ same residue
CD151 p.Tyr115= Likely benign ★ same residue
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

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-tyr115cys (accessed [today's date]).

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