Is MFRP p.Phe65= (c.195C>T) pathogenic?

MFRP p.Phe65= (c.195C>T) is classified Benign/Likely benign in MFRP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2026-01-26). Rare (popmax 0.188%, nfe); Associated with isolated microphthalmia 5.

What condition is associated with MFRP p.Phe65= (c.195C>T)?

MFRP p.Phe65= (c.195C>T) is associated with isolated microphthalmia 5 (ClinVar).

How common is MFRP p.Phe65= (c.195C>T) in the general population?

MFRP p.Phe65= (c.195C>T) is rare (popmax 0.188%, nfe) (gnomAD).

MFRP p.Phe65=

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.195C>T · rs138913508 · VCV302976

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Rare

rare (popmax 0.188%, nfe)

Conditions

isolated microphthalmia 5

⚠ Built without this gene's context — gene constraint and dosage, protein structure, pathways, panels and related-variant links were not looked up for this page. why

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
Constraint at this position
Conservation	phyloP 4.4	GERP 1.4, phastCons 1
Overall
CADD	10.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.188% European (non-Finnish) · 2,208/1,175,642 alleles

Filtering AF 0.181% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.179%

Overall 0.153% 2,460/1,604,918 alleles · rare exomes 2,292/1,452,626 · genomes 168/152,292 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.188%	532
Remaining individualsnot grpmax-eligible	0.132%	758
South Asian	0.0935%	1,070
Finnishnot grpmax-eligible	0.0572%	1,749
Admixed American	0.0411%	2,432
African / African-American	0.0347%	2,881

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.Phe65=
Coding: c.195C>T
MANE Select: NM_031433
dbSNP: rs138913508
Type: single nucleotide variant
Location: chr11:119346122 (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

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-phe65 (accessed [today's date]).

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