Is FRMD7 p.Ser23= (c.69C>T) pathogenic?

FRMD7 p.Ser23= (c.69C>T) is classified Benign in FRMD7 (ClinVar, Multiple submitters, 7 submitters; last evaluated 2026-02-02). Common (popmax 10.8%, nfe) — too common for a highly-penetrant pathogenic allele; Associated with nystagmus 1, congenital, X-linked.

What condition is associated with FRMD7 p.Ser23= (c.69C>T)?

FRMD7 p.Ser23= (c.69C>T) is associated with nystagmus 1, congenital, X-linked (ClinVar).

FRMD7 p.Ser23=

Q: How common is FRMD7 p.Ser23= (c.69C>T) in the general population?

FRMD7 p.Ser23= (c.69C>T) is common (popmax 10.8%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.69C>T · rs5930546 · VCV263089

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 7 submitters

gnomAD v4.1

Common

common (popmax 10.8%, nfe) — 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	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -8.8	GERP -7.2
Overall
CADD	0.055	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 10.8% European (non-Finnish) · 95,113/881,972 alleles

Filtering AF 10.7% ClinGen BA1/BS1 input FAF95, joint · FAF99 10.7%

Overall 9.84% 117,629/1,194,992 alleles · common exomes 108,292/1,083,347 · genomes 9,337/111,645 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	11.6%	9
European (non-Finnish)grpmax	10.8%	9
Ashkenazi Jewishnot grpmax-eligible	10%	10
Middle Eastern	9.39%	11
South Asian	9.19%	11
Remaining individualsnot grpmax-eligible	8.75%	11
Amishnot grpmax-eligible	6.13%	16
African / African-American	5.8%	17
Admixed American	4.12%	24
East Asian	0.0475%	2,107

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Ser23=
Coding: c.69C>T
MANE Select: NM_194277
dbSNP: rs5930546
Type: single nucleotide variant
Location: chrX:132100705 (GRCh38)
Structure: AlphaFold pLDDT 62.31
Residue 23: the ferm domain

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.Ser23Pro Uncertain significance ★ ⚠ 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
FRMD7 p.Leu142Arg Pathogenic/Likely 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-ser23 (accessed [today's date]).

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