Is USH1C p.Asp24fs (c.70del) pathogenic?

USH1C p.Asp24fs (c.70del) is classified Pathogenic/Likely pathogenic in USH1C (ClinVar, Multiple submitters, 2 submitters; last evaluated 2023-08-29). Very rare (popmax 8.48e-05%, nfe); Associated with autosomal recessive nonsyndromic hearing loss 18A.

What condition is associated with USH1C p.Asp24fs (c.70del)?

USH1C p.Asp24fs (c.70del) is associated with autosomal recessive nonsyndromic hearing loss 18A (ClinVar).

How common is USH1C p.Asp24fs (c.70del) in the general population?

USH1C p.Asp24fs (c.70del) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

USH1C p.Asp24fs

c.70del · rs2497241574 · VCV2679426

Pathogenic/Likely pathogenic Multiple submitters

Classification

Pathogenic/Likely pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

frameshift

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

autosomal recessive nonsyndromic hearing loss 18A

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 2 of 27
Splicing
SpliceAI	—	not assessed · substitutions only
Constraint at this position
Conservation	phyloP 7.9	GERP 2.4, phastCons 1

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,780 alleles

Overall 6.2e-05% 1/1,613,588 alleles · very rare exomes 1/1,461,592 · genomes 0/151,996 · 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: USH1C
Protein: p.Asp24fs
Coding: c.70del
MANE Select: NM_153676
dbSNP: rs2497241574
Type: Deletion
Location: chr11:17533289 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.51 · 11 PDB
Residue 24: an α-helix; the 'n-terminal domain' region

Full USH1C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autosomal recessive nonsyndromic hearing loss 18A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

USH1C c.1211-3_1232del Likely pathogenic ★★ same condition
USH1C c.2381-7_2381del Likely pathogenic ★★ same condition
USH1C c.2490+1del Likely pathogenic ★★ same condition
USH1C c.496_496+4del Pathogenic ★★ same condition
USH1C c.497-2del Pathogenic ★★ same condition
USH1C c.748_759+5del Pathogenic ★★ same condition
USH1C p.Arg80fs Pathogenic/Likely pathogenic ★★ same condition
USH1C p.Glu366fs 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/ush1c-p-asp24fs (accessed [today's date]).

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