Is OTOG p.Pro172= (c.516C>T) pathogenic?

OTOG p.Pro172= (c.516C>T) is classified Benign/Likely benign in OTOG (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-07-19). Rare (popmax 0.316%, eas); Associated with autosomal recessive nonsyndromic hearing loss 18B.

What condition is associated with OTOG p.Pro172= (c.516C>T)?

OTOG p.Pro172= (c.516C>T) is associated with autosomal recessive nonsyndromic hearing loss 18B (ClinVar).

How common is OTOG p.Pro172= (c.516C>T) in the general population?

OTOG p.Pro172= (c.516C>T) is rare (popmax 0.316%, eas) (gnomAD).

OTOG p.Pro172=

c.516C>T · rs149868055 · VCV1185111

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.316%, eas)

Conditions

autosomal recessive nonsyndromic hearing loss 18B

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 -16	GERP -5.5
Overall
CADD	0.1	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.316% East Asian · 125/39,582 alleles

Filtering AF 0.271% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.254%

Overall 0.0221% 320/1,448,734 alleles · rare exomes 271/1,296,456 · genomes 49/152,278 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.316%	317
African / African-American	0.0558%	1,791
South Asian	0.0167%	6,001
Remaining individualsnot grpmax-eligible	0.0126%	7,951
European (non-Finnish)	0.012%	8,328
Finnishnot grpmax-eligible	0.00725%	13,789
Admixed American	0.00581%	17,214

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: OTOG
Protein: p.Pro172=
Coding: c.516C>T
MANE Select: NM_001292063
dbSNP: rs149868055
Type: single nucleotide variant
Location: chr11:17553495 (GRCh38)
Gene constraint: LOEUF 1.091 · pLI <0.01 (gnomAD)
Residue 172: the vwfd 1 domain

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

Disease context

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

Similar variants

OTOG p.Arg1063Ter Pathogenic/Likely pathogenic ★★ same condition
OTOG p.Arg1153Ter Pathogenic/Likely pathogenic ★★ same condition
OTOG p.Arg1222Ter Pathogenic/Likely pathogenic ★★ same condition
OTOG p.Arg2175Ter Pathogenic/Likely pathogenic ★★ same condition
OTOG p.Arg2473Ter Pathogenic/Likely pathogenic ★★ same condition
OTOG p.Gln127Ter Pathogenic/Likely pathogenic ★★ same condition
OTOG p.Gln556Ter Pathogenic/Likely pathogenic ★★ same condition
OTOG p.Gln822Ter 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/otog-p-pro172 (accessed [today's date]).

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