Is STRC p.Leu490Pro (c.1469T>C) pathogenic?

STRC p.Leu490Pro (c.1469T>C) is classified Likely pathogenic in STRC (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-28). AlphaMissense: likely benign (0.2791); Absent from gnomAD v4.1; Associated with autosomal recessive nonsyndromic hearing loss 16.

What condition is associated with STRC p.Leu490Pro (c.1469T>C)?

STRC p.Leu490Pro (c.1469T>C) is associated with autosomal recessive nonsyndromic hearing loss 16 (ClinVar).

How common is STRC p.Leu490Pro (c.1469T>C) in the general population?

STRC p.Leu490Pro (c.1469T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about STRC p.Leu490Pro (c.1469T>C)?

AlphaMissense predicts likely benign (score 0.2791) — an in-silico prediction, not a clinical call.

STRC p.Leu490Pro

c.1469T>C · rs2507595819 · VCV2445652

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2791 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

autosomal recessive nonsyndromic hearing loss 16

Computational evidence

Protein change
AlphaMissense	0.2791	likely benign ⚠ discordant with ClinVar
REVEL	0.58	indeterminate
SaProt	LLR -7.60	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 1.9, phastCons 1
Regional constraint	o/e 0.00	constrained · MANE · 7,566 bp · p 1.3e-74 · regional, not allelic
Overall
CADD	25.4	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: STRC
Protein: p.Leu490Pro
Coding: c.1469T>C
MANE Select: NM_153700
dbSNP: rs2507595819
Type: single nucleotide variant
Location: chr15:43616097 (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

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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-leu490pro (accessed [today's date]).

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