Is MSMO1 p.Phe252Val (c.754T>G) pathogenic?

MSMO1 p.Phe252Val (c.754T>G) is classified Uncertain significance in MSMO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-14). AlphaMissense: likely pathogenic (0.9484); Absent from gnomAD v4.1; Associated with microcephaly-congenital cataract-psoriasiform dermatitis syndrome.

What condition is associated with MSMO1 p.Phe252Val (c.754T>G)?

MSMO1 p.Phe252Val (c.754T>G) is associated with microcephaly-congenital cataract-psoriasiform dermatitis syndrome (ClinVar).

How common is MSMO1 p.Phe252Val (c.754T>G) in the general population?

MSMO1 p.Phe252Val (c.754T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MSMO1 p.Phe252Val (c.754T>G)?

AlphaMissense predicts likely pathogenic (score 0.9484) — an in-silico prediction, not a clinical call.

MSMO1 p.Phe252Val

c.754T>G · VCV4056627

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9484 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

microcephaly-congenital cataract-psoriasiform dermatitis syndrome

Computational evidence

Protein change
AlphaMissense	0.9484	likely pathogenic
REVEL	0.718	pathogenic-leaning
SaProt	LLR -11.90	damaging
⇒ AlphaMissense, REVEL and SaProt all call this damaging.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 8,572 bp · p 0.0022 · regional, not allelic
Overall
CADD	27.1	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MSMO1
Protein: p.Phe252Val
Coding: c.754T>G
MANE Select: NM_006745
Type: single nucleotide variant
Location: chr4:165341818 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.13
Residue 252: the fatty acid hydroxylase domain

Full MSMO1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

microcephaly-congenital cataract-psoriasiform dermatitis syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MSMO1 p.Trp135Cys Uncertain significance ★★ ⚠ same condition
MSMO1 p.Tyr244Cys Likely pathogenic ★ same condition
MSMO1 p.Trp267Ter Uncertain significance ★ same condition
MSMO1 p.Gly246Arg Pathogenic same condition
MSMO1 p.His173Gln Pathogenic same condition
MSMO1 p.Trp267_Trp268delinsTer Uncertain significance ★ same condition
MSMO1 p.Ala60Gly Uncertain significance ★★ ⚠ same type
MSMO1 p.Asn236Ser Uncertain significance ★★ ⚠ same type

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/msmo1-p-phe252val (accessed [today's date]).

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