Is ADGRV1 p.Ile172Phe (c.514A>T) pathogenic?

ADGRV1 p.Ile172Phe (c.514A>T) is classified Uncertain significance in ADGRV1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-01-25). AlphaMissense: likely benign (0.1261); Very rare (popmax 0.00237%, eas); Associated with Usher syndrome type 2C.

What condition is associated with ADGRV1 p.Ile172Phe (c.514A>T)?

ADGRV1 p.Ile172Phe (c.514A>T) is associated with Usher syndrome type 2C (ClinVar).

How common is ADGRV1 p.Ile172Phe (c.514A>T) in the general population?

ADGRV1 p.Ile172Phe (c.514A>T) is very rare (popmax 0.00237%, eas) (gnomAD).

What do computational predictors say about ADGRV1 p.Ile172Phe (c.514A>T)?

AlphaMissense predicts likely benign (score 0.1261) — an in-silico prediction, not a clinical call.

ADGRV1 p.Ile172Phe

c.514A>T · rs2152065480 · VCV1301791

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1261 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, eas)

Conditions

Usher syndrome type 2C

Computational evidence

Protein change
AlphaMissense	0.1261	likely benign
REVEL	0.291	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	Δ0.24	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 1.7	GERP -0.82, phastCons 0.47
Regional constraint	o/e 1.00	unconstrained · MANE · 95 kb · p 0.88 · regional, not allelic
Overall
CADD	22.4	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL is an independent agreement signal.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% East Asian · 1/42,270 alleles

Overall 0.000128% 2/1,557,256 alleles · very rare exomes 2/1,404,948 · genomes 0/152,308 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00237%	42,270
European (non-Finnish)	8.69e-05%	1,150,232

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: ADGRV1
Protein: p.Ile172Phe
Coding: c.514A>T
MANE Select: NM_032119
dbSNP: rs2152065480
Type: single nucleotide variant
Location: chr5:90622657 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Residue 172: the calx-beta 2 domain

Full ADGRV1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Usher syndrome type 2C — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

ADGRV1 c.10974+1G>A Likely pathogenic ★★ same condition
ADGRV1 c.11757+2T>C Likely pathogenic ★★ same condition
ADGRV1 c.1239-1G>T Pathogenic/Likely pathogenic ★★ same condition
ADGRV1 c.13232-1G>A Pathogenic/Likely pathogenic ★★ same condition
ADGRV1 c.14972+1G>T Pathogenic/Likely pathogenic ★★ same condition
ADGRV1 c.14973-2A>G Pathogenic/Likely pathogenic ★★ same condition
ADGRV1 c.17455-2A>T Likely pathogenic ★★ same condition
ADGRV1 c.2017-1G>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/adgrv1-p-ile172phe (accessed [today's date]).

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