Is FRMD7 p.Ile511Val (c.1531A>G) pathogenic?

FRMD7 p.Ile511Val (c.1531A>G) is classified Conflicting classifications of pathogenicity in FRMD7 (ClinVar, Conflicting submitters, 5 submitters; last evaluated 2026-01-26). AlphaMissense: likely benign (0.0597); Ultra-rare (popmax 0.0566%, nfe); Associated with Inborn genetic diseases.

What condition is associated with FRMD7 p.Ile511Val (c.1531A>G)?

FRMD7 p.Ile511Val (c.1531A>G) is associated with Inborn genetic diseases (ClinVar).

How common is FRMD7 p.Ile511Val (c.1531A>G) in the general population?

FRMD7 p.Ile511Val (c.1531A>G) is ultra-rare (popmax 0.0566%, nfe) (gnomAD).

What do computational predictors say about FRMD7 p.Ile511Val (c.1531A>G)?

AlphaMissense predicts likely benign (score 0.0597) — an in-silico prediction, not a clinical call.

FRMD7 p.Ile511Val

c.1531A>G · rs199717232 · VCV1164561

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.0597 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0566%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0597	likely benign
REVEL	0.146	moderately benign-leaning
SaProt	LLR -5.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1.2	GERP -5
Regional constraint	o/e 1.00	unconstrained · MANE · 16 kb · p 0.99 · regional, not allelic
Overall
CADD	0.004	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 0.0566% European (non-Finnish) · 506/894,673 alleles

Filtering AF 0.0524% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0508%

Overall 0.0432% 522/1,209,090 alleles · ultra-rare exomes 506/1,097,671 · genomes 16/111,419 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0566%	1,768
Remaining individualsnot grpmax-eligible	0.0168%	5,950
South Asian	0.00705%	14,192
African / African-American	0.00526%	19,015
East Asian	0.00296%	33,727

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.Ile511Val
Coding: c.1531A>G
MANE Select: NM_194277
dbSNP: rs199717232
Type: single nucleotide variant
Location: chrX:132078486 (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.Ile511= Benign ★★ same residue
FRMD7 p.Ile511Thr Uncertain significance ★ ⚠ 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
FRMD7 p.Arg589Ser 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-ile511val (accessed [today's date]).

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