Is ADGRV1 p.Ile2526Val (c.7576A>G) pathogenic?

ADGRV1 p.Ile2526Val (c.7576A>G) is classified Benign in ADGRV1 (ClinVar, Multiple submitters, 10 submitters; last evaluated 2026-02-01). AlphaMissense: likely benign (0.0846); Common (popmax 6.79%, afr) — too common for a highly-penetrant pathogenic allele; Associated with Usher syndrome type 2C.

What condition is associated with ADGRV1 p.Ile2526Val (c.7576A>G)?

ADGRV1 p.Ile2526Val (c.7576A>G) is associated with Usher syndrome type 2C (ClinVar).

What do computational predictors say about ADGRV1 p.Ile2526Val (c.7576A>G)?

AlphaMissense predicts likely benign (score 0.0846) — an in-silico prediction, not a clinical call.

ADGRV1 p.Ile2526Val

Q: How common is ADGRV1 p.Ile2526Val (c.7576A>G) in the general population?

ADGRV1 p.Ile2526Val (c.7576A>G) is common (popmax 6.79%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.7576A>G · rs75191159 · VCV46376

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 10 submitters

AlphaMissense

likely benign

0.0846 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 6.79%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Usher syndrome type 2C

Computational evidence

Protein change
AlphaMissense	0.0846	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	—	not scored · why
⇒ AlphaMissense and REVEL both call this tolerated; SaProt makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.71	GERP -5.5
Regional constraint	o/e 0.96	unconstrained · MANE · 132 kb · p 0.0071 · regional, not allelic
Overall
CADD	0.034	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 6.79% African / African-American · 5,094/75,036 alleles

Filtering AF 6.63% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.57%

Overall 0.366% 5,912/1,613,950 alleles · common exomes 2,899/1,461,646 · genomes 3,013/152,304 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	6.79%	15
Remaining individualsnot grpmax-eligible	0.44%	227
Admixed American	0.432%	232
Middle Eastern	0.165%	606
European (non-Finnish)	0.0219%	4,573
South Asian	0.0132%	7,590
East Asian	0.00668%	14,961
Finnishnot grpmax-eligible	0.00156%	64,022

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.Ile2526Val
Coding: c.7576A>G
MANE Select: NM_032119
dbSNP: rs75191159
Type: single nucleotide variant
Location: chr5:90694332 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)
Residue 2526: the calx-beta 17 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 p.Ile2526Leu Conflicting classifications of pathogenicity ★ ⚠ same residue
ADGRV1 p.Ile2526Thr Uncertain significance ★ same residue
ADGRV1 p.Ile2526= Likely benign ★ same residue
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

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-ile2526val (accessed [today's date]).

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