Is FRMD7 p.Ile511= (c.1533T>C) pathogenic?

FRMD7 p.Ile511= (c.1533T>C) is classified Benign in FRMD7 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-03). Common (popmax 43.3%, afr) — too common for a highly-penetrant pathogenic allele; Associated with nystagmus 1, congenital, X-linked.

What condition is associated with FRMD7 p.Ile511= (c.1533T>C)?

FRMD7 p.Ile511= (c.1533T>C) is associated with nystagmus 1, congenital, X-linked (ClinVar).

FRMD7 p.Ile511=

Q: How common is FRMD7 p.Ile511= (c.1533T>C) in the general population?

FRMD7 p.Ile511= (c.1533T>C) is common (popmax 43.3%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1533T>C · rs5977623 · VCV263088

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 43.3%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

nystagmus 1, congenital, X-linked

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.2	GERP -2.2, phastCons 1
Overall
CADD	0.682	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 43.3% African / African-American · 24,516/56,577 alleles

Filtering AF 42.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 42.7%

Overall 29.3% 353,996/1,207,818 alleles · common exomes 319,158/1,097,680 · genomes 34,838/110,138 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	43.3%	2
Middle Eastern	39.2%	3
European (non-Finnish)	30.5%	3
Finnishnot grpmax-eligible	30%	3
Ashkenazi Jewishnot grpmax-eligible	29.7%	3
Remaining individualsnot grpmax-eligible	29.1%	3
South Asian	20.9%	5
Admixed American	13.5%	7
Amishnot grpmax-eligible	13.4%	7
East Asian	7.62%	13

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.Ile511=
Coding: c.1533T>C
MANE Select: NM_194277
dbSNP: rs5977623
Type: single nucleotide variant
Location: chrX:132078484 (GRCh38)
Structure: AlphaFold pLDDT 62.31

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

Disease context

nystagmus 1, congenital, X-linked — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

FRMD7 p.Ile511Thr Uncertain significance ★ ⚠ same residue
FRMD7 p.Ile511Val Conflicting classifications of pathogenicity ★ ⚠ same residue
FRMD7 p.Ala194Thr Pathogenic/Likely pathogenic ★★ same condition
FRMD7 p.Arg261Gln Pathogenic/Likely pathogenic ★★ same condition
FRMD7 p.Arg261Ter Pathogenic ★★ same condition
FRMD7 p.Arg304Ter Pathogenic ★★ same condition
FRMD7 p.Arg335Ter Pathogenic ★★ same condition
FRMD7 p.Gly24Arg Pathogenic ★★ 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-ile511 (accessed [today's date]).

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