Is CD151 p.Leu110Val (c.328C>G) pathogenic?

CD151 p.Leu110Val (c.328C>G) is classified Uncertain significance in CD151 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-06-12). AlphaMissense: likely benign (0.3075); Rare (popmax 0.161%, afr); Associated with epidermolysis bullosa simplex 7, with nephropathy and deafness.

What condition is associated with CD151 p.Leu110Val (c.328C>G)?

CD151 p.Leu110Val (c.328C>G) is associated with epidermolysis bullosa simplex 7, with nephropathy and deafness (ClinVar).

How common is CD151 p.Leu110Val (c.328C>G) in the general population?

CD151 p.Leu110Val (c.328C>G) is rare (popmax 0.161%, afr) (gnomAD).

What do computational predictors say about CD151 p.Leu110Val (c.328C>G)?

AlphaMissense predicts likely benign (score 0.3075) — an in-silico prediction, not a clinical call.

CD151 p.Leu110Val

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.328C>G · rs146079952 · VCV1355643

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3075 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.161%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

epidermolysis bullosa simplex 7, with nephropathy and deafness

Computational evidence

Protein change
AlphaMissense	0.3075	likely benign
REVEL	0.413	indeterminate
SaProt	LLR -9.04	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP 1, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 2,119 bp · p 0.3 · regional, not allelic
Overall
CADD	21.1	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 0.161% African / African-American · 121/75,030 alleles

Filtering AF 0.138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.129%

Overall 0.00794% 128/1,612,738 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.161%	620
Remaining individualsnot grpmax-eligible	0.008%	12,497
Admixed American	0.00167%	60,008
European (non-Finnish)	8.48e-05%	1,179,916

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.Leu110Val
Coding: c.328C>G
MANE Select: NM_004357
dbSNP: rs146079952
Type: single nucleotide variant
Location: chr11:836820 (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.Leu110Phe Uncertain significance ★ same residue
CD151 p.Leu110= 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-leu110val (accessed [today's date]).

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