Is FRMD7 p.Pro191Ser (c.571C>T) pathogenic?

FRMD7 p.Pro191Ser (c.571C>T) is classified Conflicting classifications of pathogenicity in FRMD7 (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2026-05-26). AlphaMissense: ambiguous (0.4382); Ultra-rare (popmax 0.0612%, afr); Associated with Inborn genetic diseases.

What condition is associated with FRMD7 p.Pro191Ser (c.571C>T)?

FRMD7 p.Pro191Ser (c.571C>T) is associated with Inborn genetic diseases (ClinVar).

How common is FRMD7 p.Pro191Ser (c.571C>T) in the general population?

FRMD7 p.Pro191Ser (c.571C>T) is ultra-rare (popmax 0.0612%, afr) (gnomAD).

What do computational predictors say about FRMD7 p.Pro191Ser (c.571C>T)?

AlphaMissense predicts ambiguous (score 0.4382) — an in-silico prediction, not a clinical call.

FRMD7 p.Pro191Ser

c.571C>T · rs149727630 · VCV1167983

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4382 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0612%, afr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.4382	ambiguous
REVEL	0.661	pathogenic-leaning
SaProt	LLR -9.97	tolerated
⇒ REVEL calls this damaging; SaProt does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.7	GERP 2.9, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 16 kb · p 0.99 · regional, not allelic
Overall
CADD	25.2	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 0.0612% African / African-American · 35/57,175 alleles

Filtering AF 0.0452% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0397%

Overall 0.00298% 36/1,207,123 alleles · ultra-rare exomes 13/1,095,118 · genomes 23/112,005 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0612%	1,634
Admixed American	0.00218%	45,780

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.Pro191Ser
Coding: c.571C>T
MANE Select: NM_194277
dbSNP: rs149727630
Type: single nucleotide variant
Location: chrX:132085655 (GRCh38)
Structure: AlphaFold pLDDT 62.31
Residue 191: the ferm domain

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-pro191ser (accessed [today's date]).

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