Is MFRP p.Phe235= (c.705C>T) pathogenic?

MFRP p.Phe235= (c.705C>T) is classified Conflicting classifications of pathogenicity in MFRP (ClinVar, Conflicting submitters, 2 submitters; last evaluated 2025-09-17). Ultra-rare (popmax 0.0176%, nfe); Associated with isolated microphthalmia 5.

What condition is associated with MFRP p.Phe235= (c.705C>T)?

MFRP p.Phe235= (c.705C>T) is associated with isolated microphthalmia 5, late-onset retinal degeneration (ClinVar).

How common is MFRP p.Phe235= (c.705C>T) in the general population?

MFRP p.Phe235= (c.705C>T) is ultra-rare (popmax 0.0176%, nfe) (gnomAD).

MFRP p.Phe235=

Q: How is Microphthalmia-retinitis pigmentosa-foveoschisis-optic disc drusen syndrome inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

c.705C>T · rs34190279 · VCV302967

Conflicting classifications of pathogenicity Conflicting submitters

Classification

Conflicting classifications of pathogenicity

ClinVar

Review

Conflicting submitters ★☆☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, nfe)

Conditions

isolated microphthalmia 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.21	gain · loss 0.00 · independent
Constraint at this position
Conservation	phyloP -0.022	GERP -0.75, phastCons 0.001
Overall
CADD	18.65	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0176% European (non-Finnish) · 208/1,179,000 alleles

Filtering AF 0.0156% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0149%

Overall 0.0148% 238/1,610,698 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0353%	2,836
European (non-Finnish)grpmax	0.0176%	5,668
African / African-American	0.00534%	18,728
East Asian	0.00223%	44,854
Admixed American	0.00168%	59,514
Finnishnot grpmax-eligible	0.00158%	63,160
South Asian	0.00111%	90,478

Remaining individuals 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: MFRP
Protein: p.Phe235=
Coding: c.705C>T
MANE Select: NM_001278431 · reported on NM_031433
dbSNP: rs34190279
Type: single nucleotide variant
Location: chr11:119344941 (GRCh38)

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

Disease context

isolated microphthalmia 5 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: late-onset retinal degeneration

For Microphthalmia-retinitis pigmentosa-foveoschisis-optic disc drusen syndrome (Orphanet):

Inheritance: Autosomal recessive
Onset: Adult

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/mfrp-p-phe235 (accessed [today's date]).

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