Is USH2A p.Phe2369Val (c.7105T>G) pathogenic?

USH2A p.Phe2369Val (c.7105T>G) is classified Uncertain significance in USH2A (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-06-10). AlphaMissense: likely benign (0.249); Very rare (popmax 0.005%, amr); Associated with Inborn genetic diseases.

What condition is associated with USH2A p.Phe2369Val (c.7105T>G)?

USH2A p.Phe2369Val (c.7105T>G) is associated with Inborn genetic diseases, Usher syndrome type 2A, retinitis pigmentosa 39 (ClinVar).

How common is USH2A p.Phe2369Val (c.7105T>G) in the general population?

USH2A p.Phe2369Val (c.7105T>G) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about USH2A p.Phe2369Val (c.7105T>G)?

AlphaMissense predicts likely benign (score 0.249) — an in-silico prediction, not a clinical call.

USH2A p.Phe2369Val

c.7105T>G · rs1475753019 · VCV1697080

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.249 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.249	likely benign
REVEL	0.358	indeterminate
SaProt	—	not scored · why
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 797 kb · p 0.00011 · regional, not allelic
Overall
CADD	22.2	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 0.005% Admixed American · 3/59,950 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000434% 7/1,613,628 alleles · very rare exomes 5/1,461,460 · genomes 2/152,168 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,983
Remaining individualsnot grpmax-eligible	0.0016%	62,454
European (non-Finnish)	0.000254%	393,247

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: USH2A
Protein: p.Phe2369Val
Coding: c.7105T>G
MANE Select: NM_206933
dbSNP: rs1475753019
Type: single nucleotide variant
Location: chr1:215965332 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Residue 2369: the fibronectin type-iii 10 domain

Full USH2A 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 type 2A retinitis pigmentosa 39

Similar variants

USH2A p.Phe2369fs Likely pathogenic same residue
USH2A c.12295-3T>A Pathogenic ★★★ same condition
USH2A c.8559-2A>G Pathogenic ★★★ same condition
USH2A c.8682-9A>G Pathogenic ★★★ same condition
USH2A p.Ala4740Asp Pathogenic ★★★ ⚠ same condition
USH2A p.Arg3905Cys Pathogenic ★★★ ⚠ same condition
USH2A p.Arg4192Cys Likely pathogenic ★★★ ⚠ same condition
USH2A p.Asn346His 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/ush2a-p-phe2369val (accessed [today's date]).

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