Is CD151 p.Thr41Met (c.122C>T) pathogenic?

CD151 p.Thr41Met (c.122C>T) is classified Uncertain significance in CD151 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-19). AlphaMissense: ambiguous (0.3734); Very rare (popmax 0.00134%, afr); Associated with epidermolysis bullosa simplex 7, with nephropathy and deafness.

What condition is associated with CD151 p.Thr41Met (c.122C>T)?

CD151 p.Thr41Met (c.122C>T) is associated with epidermolysis bullosa simplex 7, with nephropathy and deafness (ClinVar).

How common is CD151 p.Thr41Met (c.122C>T) in the general population?

CD151 p.Thr41Met (c.122C>T) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about CD151 p.Thr41Met (c.122C>T)?

AlphaMissense predicts ambiguous (score 0.3734) — an in-silico prediction, not a clinical call.

CD151 p.Thr41Met

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.122C>T · VCV3574082

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3734 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Conditions

epidermolysis bullosa simplex 7, with nephropathy and deafness

Computational evidence

Protein change
AlphaMissense	0.3734	ambiguous
REVEL	0.602	indeterminate
SaProt	LLR -7.83	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 2, phastCons 1
Regional constraint	o/e 0.94	unconstrained · MANE · 2,119 bp · p 0.3 · regional, not allelic
Overall
CADD	28.4	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 · 1/74,868 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.00031% 5/1,612,394 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,868
European (non-Finnish)	0.000339%	294,963

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.Thr41Met
Coding: c.122C>T
MANE Select: NM_004357
Type: single nucleotide variant
Location: chr11:836288 (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.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-thr41met (accessed [today's date]).

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