Is FRMD7 p.Pro614Arg (c.1841C>G) pathogenic?

FRMD7 p.Pro614Arg (c.1841C>G) is classified Uncertain significance in FRMD7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-10-02). AlphaMissense: likely benign (0.2098); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with FRMD7 p.Pro614Arg (c.1841C>G)?

FRMD7 p.Pro614Arg (c.1841C>G) is associated with Inborn genetic diseases (ClinVar).

How common is FRMD7 p.Pro614Arg (c.1841C>G) in the general population?

FRMD7 p.Pro614Arg (c.1841C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FRMD7 p.Pro614Arg (c.1841C>G)?

AlphaMissense predicts likely benign (score 0.2098) — an in-silico prediction, not a clinical call.

FRMD7 p.Pro614Arg

c.1841C>G · rs2520692561 · VCV2090748

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.2098 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.2098	likely benign
REVEL	0.687	pathogenic-leaning
SaProt	LLR -6.83	tolerated
⇒ REVEL calls this damaging; AlphaMissense and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 4.3, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 16 kb · p 0.99 · regional, not allelic
Overall
CADD	24.9	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.Pro614Arg
Coding: c.1841C>G
MANE Select: NM_194277
dbSNP: rs2520692561
Type: single nucleotide variant
Location: chrX:132078176 (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-pro614arg (accessed [today's date]).

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