Is MFRP p.Phe414= (c.1242C>T) pathogenic?

MFRP p.Phe414= (c.1242C>T) is classified Likely benign in MFRP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-01-29). Ultra-rare (popmax 0.0154%, sas); Associated with isolated microphthalmia 5.

What condition is associated with MFRP p.Phe414= (c.1242C>T)?

MFRP p.Phe414= (c.1242C>T) is associated with isolated microphthalmia 5 (ClinVar).

How common is MFRP p.Phe414= (c.1242C>T) in the general population?

MFRP p.Phe414= (c.1242C>T) is ultra-rare (popmax 0.0154%, sas) (gnomAD).

MFRP p.Phe414=

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.1242C>T · rs1313013945 · VCV763779

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0154%, sas)

Conditions

isolated microphthalmia 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.065	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.27	loss · gain 0.00 · independent
Constraint at this position
Conservation	phyloP 3	GERP -1.1, phastCons 1
Overall
CADD	7.857	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0154% South Asian · 14/91,076 alleles

Filtering AF 0.0092% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00735%

Overall 0.0013% 19/1,460,714 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0154%	6,505
European (non-Finnish)	0.000424%	235,985

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.Phe414=
Coding: c.1242C>T
MANE Select: NM_001278431 · reported on NM_031433
dbSNP: rs1313013945
Type: single nucleotide variant
Location: chr11:119342886 (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-phe414 (accessed [today's date]).

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