Is MFRP p.Pro462= (c.1386A>T) pathogenic?

MFRP p.Pro462= (c.1386A>T) is classified Uncertain significance in MFRP (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-18). Very rare (popmax 8.48e-05%, nfe); Associated with isolated microphthalmia 5.

What condition is associated with MFRP p.Pro462= (c.1386A>T)?

MFRP p.Pro462= (c.1386A>T) is associated with isolated microphthalmia 5 (ClinVar).

How common is MFRP p.Pro462= (c.1386A>T) in the general population?

MFRP p.Pro462= (c.1386A>T) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

MFRP p.Pro462=

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.1386A>T · rs2135368869 · VCV1485878

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Conditions

isolated microphthalmia 5

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.094	moderately benign-leaning
Splicing
SpliceAI	—	not looked up on this page · why
Pangolin	Δ0.38	loss · gain 0.00 · independent
Constraint at this position
Conservation	phyloP 0.39	GERP 0.34, phastCons 1
Overall
CADD	14.68	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 8.48e-05% European (non-Finnish) · 1/1,179,804 alleles

Overall 6.2e-05% 1/1,613,094 alleles · very rare exomes 1/1,460,952 · genomes 0/152,142 · joint denominator

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.Pro462=
Coding: c.1386A>T
MANE Select: NM_031433
dbSNP: rs2135368869
Type: single nucleotide variant
Location: chr11:119342597 (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-pro462 (accessed [today's date]).

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