Is FRMD7 p.Phe16Ser (c.47T>C) pathogenic?

FRMD7 p.Phe16Ser (c.47T>C) is classified Pathogenic in FRMD7 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-07-22). AlphaMissense: likely pathogenic (0.9943); Absent from gnomAD v4.1.

How common is FRMD7 p.Phe16Ser (c.47T>C) in the general population?

FRMD7 p.Phe16Ser (c.47T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about FRMD7 p.Phe16Ser (c.47T>C)?

AlphaMissense predicts likely pathogenic (score 0.9943) — an in-silico prediction, not a clinical call.

FRMD7 p.Phe16Ser

c.47T>C · rs2124046017 · VCV1219261

Pathogenic Multiple submitters

Classification

Pathogenic

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9943 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9943	likely pathogenic ✓ concordant with ClinVar · top 3% in FRMD7
REVEL	0.816	moderately pathogenic-leaning
SaProt	LLR -14.44	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 11	GERP 4.1, phastCons 1
Regional constraint	o/e 1.11	unconstrained · MANE · 27 kb · p 0.61 · regional, not allelic
Overall
CADD	24.3	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.Phe16Ser
Coding: c.47T>C
MANE Select: NM_194277
dbSNP: rs2124046017
Type: single nucleotide variant
Location: chrX:132127798 (GRCh38)
Structure: AlphaFold pLDDT 62.31
Residue 16: the ferm domain; a UniProt-annotated variant site (in nys1)

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

Similar variants

FRMD7 c.906-2A>G Likely pathogenic ★★ same type
FRMD7 p.Ala194Thr Pathogenic/Likely pathogenic ★★ same type
FRMD7 p.Arg261Gln Pathogenic/Likely pathogenic ★★ same type
FRMD7 p.Arg261Ter Pathogenic ★★ same type
FRMD7 p.Arg304Ter Pathogenic ★★ same type
FRMD7 p.Arg335Ter Pathogenic ★★ same type
FRMD7 p.Gly24Arg Pathogenic ★★ same type
FRMD7 p.Gly296Arg Pathogenic ★★ same type

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-phe16ser (accessed [today's date]).

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