Is ADGRV1 p.Ser3336Phe (c.10007C>T) pathogenic?

ADGRV1 p.Ser3336Phe (c.10007C>T) is classified Conflicting classifications of pathogenicity in ADGRV1 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2026-01-27). AlphaMissense: likely benign (0.2196); Ultra-rare (popmax 0.0542%, amr); Associated with Inborn genetic diseases.

What condition is associated with ADGRV1 p.Ser3336Phe (c.10007C>T)?

ADGRV1 p.Ser3336Phe (c.10007C>T) is associated with Inborn genetic diseases, Usher syndrome (ClinVar).

How common is ADGRV1 p.Ser3336Phe (c.10007C>T) in the general population?

ADGRV1 p.Ser3336Phe (c.10007C>T) is ultra-rare (popmax 0.0542%, amr) (gnomAD).

What do computational predictors say about ADGRV1 p.Ser3336Phe (c.10007C>T)?

AlphaMissense predicts likely benign (score 0.2196) — an in-silico prediction, not a clinical call.

ADGRV1 p.Ser3336Phe

c.10007C>T · rs781697491 · VCV1367599

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2196 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0542%, amr)

Missense predictors

0/2 damaging

AlphaMissense, REVEL · SaProt no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2196	likely benign
REVEL	0.154	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 4.9	GERP 0.76, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 132 kb · p 0.0071 · regional, not allelic
Overall
CADD	21.1	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 0.0542% Admixed American · 26/47,940 alleles

Filtering AF 0.038% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0326%

Overall 0.00194% 30/1,544,088 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0542%	1,844
Remaining individualsnot grpmax-eligible	0.00501%	19,957
European (non-Finnish)	8.77e-05%	1,140,348

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.Ser3336Phe
Coding: c.10007C>T
MANE Select: NM_032119
dbSNP: rs781697491
Type: single nucleotide variant
Location: chr5:90725186 (GRCh38)
Gene constraint: LOEUF 0.637 · pLI <0.01 (gnomAD)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Usher syndrome

Similar variants

ADGRV1 c.14973-2A>G Pathogenic/Likely pathogenic ★★ same condition
ADGRV1 p.Arg2377Gln Pathogenic/Likely pathogenic ★★ same condition
ADGRV1 p.Arg3147Ter Pathogenic/Likely pathogenic ★★ same condition
ADGRV1 p.Arg4071Ter Pathogenic/Likely pathogenic ★★ same condition
ADGRV1 p.Arg5772Ter Pathogenic ★★ same condition
ADGRV1 p.Gln2204Ter Pathogenic/Likely pathogenic ★★ same condition
ADGRV1 p.Gln2301Ter Pathogenic/Likely pathogenic ★★ same condition
ADGRV1 p.Gln4777Ter 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-ser3336phe (accessed [today's date]).

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