Is MFRP p.Pro166Ala (c.496C>G) pathogenic?

MFRP p.Pro166Ala (c.496C>G) is classified Benign/Likely benign in MFRP (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-30). AlphaMissense: likely benign (0.118); Rare (popmax 0.399%, eas); Associated with isolated microphthalmia 5.

What condition is associated with MFRP p.Pro166Ala (c.496C>G)?

MFRP p.Pro166Ala (c.496C>G) is associated with isolated microphthalmia 5, late-onset retinal degeneration (ClinVar).

How common is MFRP p.Pro166Ala (c.496C>G) in the general population?

MFRP p.Pro166Ala (c.496C>G) is rare (popmax 0.399%, eas) (gnomAD).

What do computational predictors say about MFRP p.Pro166Ala (c.496C>G)?

AlphaMissense predicts likely benign (score 0.118) — an in-silico prediction, not a clinical call.

MFRP p.Pro166Ala

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.496C>G · rs145285193 · VCV302970

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.118 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.399%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

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
AlphaMissense	0.118	likely benign
REVEL	0.161	moderately benign-leaning
SaProt	LLR -7.59	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.3	GERP -2.8, phastCons 1
Regional constraint	o/e 1.14	unconstrained · MANE · 4,962 bp · p 0.00017 · regional, not allelic
Overall
CADD	19.04	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.399% East Asian · 179/44,878 alleles

Filtering AF 0.351% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.333%

Overall 0.0142% 229/1,614,054 alleles · rare exomes 194/1,461,708 · genomes 35/152,346 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.399%	251
Remaining individualsnot grpmax-eligible	0.056%	1,786
Admixed American	0.00666%	15,005
South Asian	0.00549%	18,216
African / African-American	0.00533%	18,765
European (non-Finnish)	0.000169%	590,019

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.Pro166Ala
Coding: c.496C>G
MANE Select: NM_031433
dbSNP: rs145285193
Type: single nucleotide variant
Location: chr11:119345565 (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

Also linked: late-onset retinal degeneration

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-pro166ala (accessed [today's date]).

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