Is STRC p.Phe60Ser (c.179T>C) pathogenic?

STRC p.Phe60Ser (c.179T>C) is classified Benign/Likely benign in STRC (ClinVar, Multiple submitters, 10 submitters; last evaluated 2021-12-17). AlphaMissense: likely benign (0.0435); Common (popmax 65.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with autosomal recessive nonsyndromic hearing loss 16.

What condition is associated with STRC p.Phe60Ser (c.179T>C)?

STRC p.Phe60Ser (c.179T>C) is associated with autosomal recessive nonsyndromic hearing loss 16 (ClinVar).

What do computational predictors say about STRC p.Phe60Ser (c.179T>C)?

AlphaMissense predicts likely benign (score 0.0435) — an in-silico prediction, not a clinical call.

STRC p.Phe60Ser

Q: How common is STRC p.Phe60Ser (c.179T>C) in the general population?

STRC p.Phe60Ser (c.179T>C) is common (popmax 65.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.179T>C · rs2729509 · VCV156030

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0435 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 65.3%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 16

Computational evidence

Protein change
AlphaMissense	0.0435	likely benign
REVEL	0.149	moderately benign-leaning
SaProt	LLR -4.96	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 0.73, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	17.4	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 65.3% African / African-American · 21,354/32,688 alleles

Filtering AF 64.6% ClinGen BA1/BS1 input FAF95, joint · FAF99 64.3%

Overall 30.7% 197,533/644,080 alleles · common exomes 167,071/555,480 · genomes 30,462/88,600 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	65.3%	2
Middle Eastern	40.4%	2
Ashkenazi Jewishnot grpmax-eligible	37.8%	3
South Asian	36.8%	3
East Asian	32.7%	3
Remaining individualsnot grpmax-eligible	32.6%	3
Admixed American	31.5%	3
European (non-Finnish)	27.3%	4
Amishnot grpmax-eligible	19.7%	5
Finnishnot grpmax-eligible	18.2%	5

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.Phe60Ser
Coding: c.179T>C
MANE Select: NM_153700
dbSNP: rs2729509
Type: single nucleotide variant
Location: chr15:43618242 (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 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
STRC p.Arg1468Ter 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-phe60ser (accessed [today's date]).

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