Is MFRP p.Asp352= (c.1056C>T) pathogenic?

MFRP p.Asp352= (c.1056C>T) is classified Likely benign in MFRP (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-07-09). Ultra-rare (popmax 0.024%, afr); Associated with isolated microphthalmia 5.

What condition is associated with MFRP p.Asp352= (c.1056C>T)?

MFRP p.Asp352= (c.1056C>T) is associated with isolated microphthalmia 5 (ClinVar).

How common is MFRP p.Asp352= (c.1056C>T) in the general population?

MFRP p.Asp352= (c.1056C>T) is ultra-rare (popmax 0.024%, afr) (gnomAD).

MFRP p.Asp352=

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.1056C>T · rs139725826 · VCV1087413

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.024%, afr)

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
Constraint at this position
Conservation	phyloP -12	GERP -3.1
Overall
CADD	0.227	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.024% African / African-American · 18/74,948 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00291% 47/1,613,860 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.024%	4,164
East Asian	0.0111%	8,972
Admixed American	0.00667%	15,003
Remaining individualsnot grpmax-eligible	0.0048%	20,835
European (non-Finnish)	0.00144%	69,412

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.Asp352=
Coding: c.1056C>T
MANE Select: NM_001278431 · reported on NM_031433
dbSNP: rs139725826
Type: single nucleotide variant
Location: chr11:119343884 (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-asp352 (accessed [today's date]).

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