Is STRC p.Val1589Phe (c.4765G>T) pathogenic?

STRC p.Val1589Phe (c.4765G>T) is classified Uncertain significance in STRC (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-07-01). AlphaMissense: likely benign (0.1299); Very rare (popmax 0.00672%, eas); Associated with autosomal recessive nonsyndromic hearing loss 16.

What condition is associated with STRC p.Val1589Phe (c.4765G>T)?

STRC p.Val1589Phe (c.4765G>T) is associated with autosomal recessive nonsyndromic hearing loss 16 (ClinVar).

How common is STRC p.Val1589Phe (c.4765G>T) in the general population?

STRC p.Val1589Phe (c.4765G>T) is very rare (popmax 0.00672%, eas) (gnomAD).

What do computational predictors say about STRC p.Val1589Phe (c.4765G>T)?

AlphaMissense predicts likely benign (score 0.1299) — an in-silico prediction, not a clinical call.

STRC p.Val1589Phe

c.4765G>T · rs147963245 · VCV1185131

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1299 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00672%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autosomal recessive nonsyndromic hearing loss 16

Computational evidence

Protein change
AlphaMissense	0.1299	likely benign
REVEL	0.096	moderately benign-leaning
SaProt	LLR -6.74	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 4.1	GERP -1.3, phastCons 1
Regional constraint	o/e 0.44	unconstrained · MANE · 511 bp · p 2.1e-05 · regional, not allelic
Overall
CADD	19.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00672% East Asian · 3/44,650 alleles

Filtering AF 0.00178% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000894%

Overall 0.000187% 3/1,606,886 alleles · very rare exomes 2/1,461,114 · genomes 1/145,772 · joint denominator

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.Val1589Phe
Coding: c.4765G>T
MANE Select: NM_153700
dbSNP: rs147963245
Type: single nucleotide variant
Location: chr15:43600951 (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.Val1589Ile Conflicting classifications of pathogenicity ★ ⚠ 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-val1589phe (accessed [today's date]).

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