Is STRC p.Val724fs (c.2171_2174del) pathogenic?

STRC p.Val724fs (c.21712174del) is classified Pathogenic in STRC (ClinVar, Multiple submitters, 3 submitters; last evaluated 2022-11-10). Very rare (popmax 0.0094%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 16.

What condition is associated with STRC p.Val724fs (c.2171_2174del)?

STRC p.Val724fs (c.2171_2174del) is associated with autosomal recessive nonsyndromic hearing loss 16 (ClinVar).

How common is STRC p.Val724fs (c.2171_2174del) in the general population?

STRC p.Val724fs (c.2171_2174del) is very rare (popmax 0.0094%, nfe) (gnomAD).

STRC p.Val724fs

c.2171_2174del · rs786200883 · VCV4344

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0094%, 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.
Consequence	frameshift	predicted loss-of-function
NMD	predicted	premature termination codon in exon 5 of 29
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree
Region caveats
Repeat context	seg dup	· reads may not map uniquely · confidence, not pathogenicity

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0094% European (non-Finnish) · 39/414,804 alleles

Filtering AF 0.00703% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00617%

Overall 0.00786% 50/636,356 alleles · very rare exomes 44/573,962 · genomes 6/62,394 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0185%	5,395
Remaining individualsnot grpmax-eligible	0.0109%	9,212
European (non-Finnish)grpmax	0.0094%	10,636

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val724fs
Coding: c.2171_2174del
MANE Select: NM_153700
dbSNP: rs786200883
Type: Deletion
Location: chr15:43614436 (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.Cys1599fs Pathogenic ★★ same condition
STRC p.Glu1504fs Pathogenic/Likely pathogenic ★★ same condition
STRC p.Leu1417_Leu1418insTer Pathogenic/Likely pathogenic ★★ same condition
STRC c.3499_4701+1del Pathogenic ★ same condition
STRC p.Gly667fs Likely pathogenic ★ same condition
STRC p.Phe1495fs Pathogenic ★ same condition
STRC p.Pro1043fs Likely pathogenic ★ same condition
STRC p.Val724= Likely benign ★ same residue

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-val724fs (accessed [today's date]).

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