Is USH1C p.Pro704= (c.2112A>G) pathogenic?

USH1C p.Pro704= (c.2112A>G) is classified Likely benign in USH1C (ClinVar, Multiple submitters, 6 submitters; last evaluated 2024-08-07). Rare (popmax 0.105%, eas); Associated with Usher syndrome type 1C.

What condition is associated with USH1C p.Pro704= (c.2112A>G)?

USH1C p.Pro704= (c.2112A>G) is associated with Usher syndrome type 1C, Usher syndrome type 1, autosomal recessive nonsyndromic hearing loss 18A (ClinVar).

How common is USH1C p.Pro704= (c.2112A>G) in the general population?

USH1C p.Pro704= (c.2112A>G) is rare (popmax 0.105%, eas) (gnomAD).

USH1C p.Pro704=

c.2112A>G · rs199532754 · VCV179845

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 6 submitters

gnomAD v4.1

Rare

rare (popmax 0.105%, eas)

Conditions

Usher syndrome type 1C

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.44	GERP -0.002, phastCons 0.98
Overall
CADD	7.811	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.105% East Asian · 47/44,884 alleles

Filtering AF 0.0808% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0725%

Overall 0.00409% 66/1,614,160 alleles · rare exomes 57/1,461,822 · genomes 9/152,338 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.105%	955
Remaining individualsnot grpmax-eligible	0.0272%	3,677
Admixed American	0.00333%	30,014

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.Pro704=
Coding: c.2112A>G
MANE Select: NM_153676
dbSNP: rs199532754
Type: single nucleotide variant
Location: chr11:17505851 (GRCh38)
Gene constraint: LOEUF 0.876 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 79.51 · 11 PDB

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

Disease context

Usher syndrome type 1C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome type 1 autosomal recessive nonsyndromic hearing loss 18A

Similar variants

USH1C c.1020-2A>C Likely pathogenic ★★ same condition
USH1C c.104+1G>A Pathogenic/Likely pathogenic ★★ same condition
USH1C c.104+5G>C Likely pathogenic ★★ same condition
USH1C c.105-2A>G Pathogenic/Likely pathogenic ★★ same condition
USH1C c.2185-1G>A Likely pathogenic ★★ same condition
USH1C c.2227-1G>T Pathogenic/Likely pathogenic ★★ same condition
USH1C c.2280+2T>C Likely pathogenic ★★ same condition
USH1C c.248+1G>A 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-pro704 (accessed [today's date]).

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