Is CD151 p.Arg165Ter (c.493C>T) pathogenic?

CD151 p.Arg165Ter (c.493C>T) is classified Conflicting classifications of pathogenicity in CD151 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2025-08-14). Very rare (popmax 0.00223%, eas); Associated with epidermolysis bullosa simplex 7, with nephropathy and deafness.

What condition is associated with CD151 p.Arg165Ter (c.493C>T)?

CD151 p.Arg165Ter (c.493C>T) is associated with epidermolysis bullosa simplex 7, with nephropathy and deafness (ClinVar).

How common is CD151 p.Arg165Ter (c.493C>T) in the general population?

CD151 p.Arg165Ter (c.493C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

CD151 p.Arg165Ter

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.493C>T · rs759213580 · VCV1028736

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

epidermolysis bullosa simplex 7, with nephropathy and deafness

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function
NMD	predicted	premature termination codon in exon 7 of 9
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.1	GERP -3.3
Overall
CADD	36.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,870 alleles

Filtering AF 0.000688% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000539%

Overall 0.0011% 16/1,460,622 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,870
European (non-Finnish)	0.00119%	84,283
South Asian	0.0011%	91,070

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.Arg165Ter
Coding: c.493C>T
MANE Select: NM_004357
dbSNP: rs759213580
Type: single nucleotide variant
Location: chr11:837496 (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.Arg165Gln Uncertain significance ★★ ⚠ 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
CD151 p.Arg133Cys 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-arg165ter (accessed [today's date]).

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