Is FRMD7 p.Pro492Ser (c.1474C>T) pathogenic?

FRMD7 p.Pro492Ser (c.1474C>T) is classified Conflicting classifications of pathogenicity in FRMD7 (ClinVar, Conflicting submitters, 4 submitters; last evaluated 2025-12-16). AlphaMissense: likely benign (0.1016); Ultra-rare (popmax 0.0106%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FRMD7 p.Pro492Ser (c.1474C>T)?

FRMD7 p.Pro492Ser (c.1474C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FRMD7 p.Pro492Ser (c.1474C>T) in the general population?

FRMD7 p.Pro492Ser (c.1474C>T) is ultra-rare (popmax 0.0106%, nfe) (gnomAD).

What do computational predictors say about FRMD7 p.Pro492Ser (c.1474C>T)?

AlphaMissense predicts likely benign (score 0.1016) — an in-silico prediction, not a clinical call.

FRMD7 p.Pro492Ser

c.1474C>T · rs143451711 · VCV755905

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.1016 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0106%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1016	likely benign
REVEL	0.281	benign-leaning
SaProt	LLR -6.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Pangolin	Δ0.21	gain · loss 0.00 · not in the SpliceAI release · independent
Constraint at this position
Conservation	phyloP 6.7	GERP 4.4, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 16 kb · p 0.99 · regional, not allelic
Overall
CADD	16.82	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

Grpmax group 0.0106% European (non-Finnish) · 95/894,952 alleles

Filtering AF 0.00886% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00823%

Overall 0.00835% 101/1,209,623 alleles · ultra-rare exomes 100/1,097,887 · genomes 1/111,736 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0106%	9,421
Remaining individualsnot grpmax-eligible	0.00841%	11,896
Admixed American	0.00219%	45,722
African / African-American	0.00175%	57,109

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: FRMD7
Protein: p.Pro492Ser
Coding: c.1474C>T
MANE Select: NM_194277
dbSNP: rs143451711
Type: single nucleotide variant
Location: chrX:132078543 (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.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
FRMD7 p.Arg589Ser Uncertain significance ★★ same condition
FRMD7 p.Arg600Cys Uncertain significance ★★ ⚠ same condition
FRMD7 p.Asp652Asn 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-pro492ser (accessed [today's date]).

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