Is FRMD7 p.Pro493Ser (c.1477C>T) pathogenic?

FRMD7 p.Pro493Ser (c.1477C>T) is classified Uncertain significance in FRMD7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-04). AlphaMissense: likely benign (0.0814); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FRMD7 p.Pro493Ser (c.1477C>T)?

FRMD7 p.Pro493Ser (c.1477C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FRMD7 p.Pro493Ser (c.1477C>T) in the general population?

FRMD7 p.Pro493Ser (c.1477C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FRMD7 p.Pro493Ser (c.1477C>T)?

AlphaMissense predicts likely benign (score 0.0814) — an in-silico prediction, not a clinical call.

FRMD7 p.Pro493Ser

c.1477C>T · rs2520699610 · VCV2532383

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0814 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0814	likely benign
REVEL	0.32	indeterminate
SaProt	LLR -6.21	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 8.6	GERP 3.6, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 16 kb · p 0.99 · regional, not allelic
Overall
CADD	18.61	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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.Pro493Ser
Coding: c.1477C>T
MANE Select: NM_194277
dbSNP: rs2520699610
Type: single nucleotide variant
Location: chrX:132078540 (GRCh38)
Structure: AlphaFold pLDDT 62.31

Full FRMD7 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

Similar variants

FRMD7 p.Pro493Leu Uncertain significance ★ ⚠ same residue
FRMD7 p.Pro493Thr Uncertain significance ★★ ⚠ same residue
FRMD7 p.Pro493= Likely benign ★★ same residue
FRMD7 p.Ala577Val Uncertain significance ★★ ⚠ same condition
FRMD7 p.Ala642Thr Uncertain significance ★★ ⚠ same condition
FRMD7 p.Arg110Gly Uncertain significance ★★ ⚠ same condition
FRMD7 p.Arg110Ser Uncertain significance ★★ same condition
FRMD7 p.Arg468Cys Uncertain significance ★★ ⚠ 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-pro493ser (accessed [today's date]).

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