Is FRMD7 p.Val495Phe (c.1483G>T) pathogenic?

FRMD7 p.Val495Phe (c.1483G>T) is classified Likely pathogenic in FRMD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-20). AlphaMissense: likely benign (0.142); Absent from gnomAD v4.1; Associated with FRMD7-related disorders.

What condition is associated with FRMD7 p.Val495Phe (c.1483G>T)?

FRMD7 p.Val495Phe (c.1483G>T) is associated with FRMD7-related disorders (ClinVar).

How common is FRMD7 p.Val495Phe (c.1483G>T) in the general population?

FRMD7 p.Val495Phe (c.1483G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FRMD7 p.Val495Phe (c.1483G>T)?

AlphaMissense predicts likely benign (score 0.142) — an in-silico prediction, not a clinical call.

FRMD7 p.Val495Phe

c.1483G>T · VCV4952879

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.142 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

FRMD7-related disorders

Computational evidence

Protein change
AlphaMissense	0.142	likely benign ⚠ discordant with ClinVar
REVEL	0.533	indeterminate
SaProt	LLR -7.65	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.7	GERP 4.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 16 kb · p 0.99 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: FRMD7
Protein: p.Val495Phe
Coding: c.1483G>T
MANE Select: NM_194277
Type: single nucleotide variant
Location: chrX:132078534 (GRCh38)
Structure: AlphaFold pLDDT 62.31

Full FRMD7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

FRMD7-related disorders

Similar variants

FRMD7 c.906-2A>G Likely pathogenic ★★ same condition
FRMD7 p.Arg261Ter Pathogenic ★★ same condition
FRMD7 p.Arg304Ter Pathogenic ★★ same condition
FRMD7 p.Arg335Ter Pathogenic ★★ same condition
FRMD7 p.Leu142Arg Pathogenic/Likely pathogenic ★★ same condition
FRMD7 p.Leu231Val Pathogenic ★★ ⚠ same condition
FRMD7 c.284+1G>A Pathogenic ★ same condition
FRMD7 p.Ala266Pro 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/frmd7-p-val495phe (accessed [today's date]).

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