Is STRC p.Pro166= (c.498G>A) pathogenic?

STRC p.Pro166= (c.498G>A) is classified Benign/Likely benign in STRC (ClinVar, Multiple submitters, 7 submitters; last evaluated 2025-08-01). Rare (popmax 0.763%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 16.

What condition is associated with STRC p.Pro166= (c.498G>A)?

STRC p.Pro166= (c.498G>A) is associated with autosomal recessive nonsyndromic hearing loss 16 (ClinVar).

How common is STRC p.Pro166= (c.498G>A) in the general population?

STRC p.Pro166= (c.498G>A) is rare (popmax 0.763%, nfe) (gnomAD).

STRC p.Pro166=

c.498G>A · rs139848805 · VCV165324

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Rare

rare (popmax 0.763%, nfe)

Conditions

autosomal recessive nonsyndromic hearing loss 16

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 0.25	GERP -2.8, phastCons 0.39
Overall
CADD	12.86	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.763% European (non-Finnish) · 8,958/1,173,982 alleles

Filtering AF 0.75% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.744%

Overall 0.641% 10,305/1,607,738 alleles · rare exomes 9,594/1,455,708 · genomes 711/152,030 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.763%	131
Finnishnot grpmax-eligible	0.76%	132
Remaining individualsnot grpmax-eligible	0.539%	185
Ashkenazi Jewishnot grpmax-eligible	0.5%	200
Admixed American	0.215%	465
African / African-American	0.188%	532
Amishnot grpmax-eligible	0.11%	910
South Asian	0.089%	1,124
East Asian	0.0535%	1,871
Middle Eastern	0.0165%	6,054

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.Pro166=
Coding: c.498G>A
MANE Select: NM_153700
dbSNP: rs139848805
Type: single nucleotide variant
Location: chr15:43617923 (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

autosomal recessive nonsyndromic hearing loss 16 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

STRC p.Pro166Leu Uncertain significance ★ ⚠ same residue
STRC c.4219-1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC c.4701+1G>A Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1073Ter Pathogenic ★★ same condition
STRC p.Arg1154Ter Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1224Ter Pathogenic ★★ same condition
STRC p.Arg1338Ter Pathogenic/Likely pathogenic ★★ same condition
STRC p.Arg1451Ter Pathogenic/Likely 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-pro166 (accessed [today's date]).

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