Is MFRP p.Ala413= (c.1239C>T) pathogenic?

MFRP p.Ala413= (c.1239C>T) is classified Likely benign in MFRP (ClinVar, Single submitter, 1 submitter; last evaluated 2021-11-22). Very rare (popmax 0.00237%, nfe); Associated with isolated microphthalmia 5.

What condition is associated with MFRP p.Ala413= (c.1239C>T)?

MFRP p.Ala413= (c.1239C>T) is associated with isolated microphthalmia 5 (ClinVar).

How common is MFRP p.Ala413= (c.1239C>T) in the general population?

MFRP p.Ala413= (c.1239C>T) is very rare (popmax 0.00237%, nfe) (gnomAD).

MFRP p.Ala413=

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.1239C>T · rs752871438 · VCV1547596

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Conditions

isolated microphthalmia 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.098	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 2.1	GERP 0.26, phastCons 1
Overall
CADD	8.668	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00237% European (non-Finnish) · 28/1,179,944 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.0018% 29/1,612,950 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00237%	42,141
Remaining individualsnot grpmax-eligible	0.0016%	62,450

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.Ala413=
Coding: c.1239C>T
MANE Select: NM_001278431 · reported on NM_031433
dbSNP: rs752871438
Type: single nucleotide variant
Location: chr11:119342889 (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-ala413 (accessed [today's date]).

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