Is STRC p.Pro1265= (c.3795G>A) pathogenic?

STRC p.Pro1265= (c.3795G>A) is classified Conflicting classifications of pathogenicity in STRC (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-05-01). Rare (popmax 0.115%, sas); Associated with Rare genetic deafness.

What condition is associated with STRC p.Pro1265= (c.3795G>A)?

STRC p.Pro1265= (c.3795G>A) is associated with Rare genetic deafness (ClinVar).

How common is STRC p.Pro1265= (c.3795G>A) in the general population?

STRC p.Pro1265= (c.3795G>A) is rare (popmax 0.115%, sas) (gnomAD).

STRC p.Pro1265=

c.3795G>A · rs2614833 · VCV3048594

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.115%, sas)

Conditions

Rare genetic deafness

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP -1.2, phastCons 0.95
Overall
CADD	10.56	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.115% South Asian · 102/89,000 alleles

Filtering AF 0.0966% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0898%

Overall 0.00937% 150/1,600,766 alleles · rare exomes 133/1,448,910 · genomes 17/151,856 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.115%	873
Remaining individualsnot grpmax-eligible	0.0194%	5,166
Middle Eastern	0.0166%	6,040
African / African-American	0.00803%	12,456
East Asian	0.00448%	22,346
European (non-Finnish)	0.0023%	43,428

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: STRC
Protein: p.Pro1265=
Coding: c.3795G>A
MANE Select: NM_153700
dbSNP: rs2614833
Type: single nucleotide variant
Location: chr15:43605399 (GRCh38)
Gene constraint: LOEUF 0.713 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.21

Full STRC gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Rare genetic deafness — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STRC p.Pro1265Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
STRC p.Arg1224Ter Pathogenic ★★ same condition
STRC p.Arg1468Ter Pathogenic ★★ same condition
STRC p.Glu1399Ter Pathogenic ★★ same condition
STRC c.4375+1G>A Pathogenic ★ same condition
STRC c.4702-2A>C Likely pathogenic ★ same condition
STRC p.Arg127Ter Pathogenic ★ same condition
STRC p.Gln1165Ter Pathogenic ★ 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/strc-p-pro1265 (accessed [today's date]).

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