Is MSMO1 p.Phe65Leu (c.195C>A) pathogenic?

MSMO1 p.Phe65Leu (c.195C>A) is classified Uncertain significance in MSMO1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-21). AlphaMissense: ambiguous (0.4253); Very rare (popmax 0.00171%, amr).

How common is MSMO1 p.Phe65Leu (c.195C>A) in the general population?

MSMO1 p.Phe65Leu (c.195C>A) is very rare (popmax 0.00171%, amr) (gnomAD).

What do computational predictors say about MSMO1 p.Phe65Leu (c.195C>A)?

AlphaMissense predicts ambiguous (score 0.4253) — an in-silico prediction, not a clinical call.

MSMO1 p.Phe65Leu

c.195C>A · rs1172820720 · VCV3012308

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4253 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00171%, amr)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4253	ambiguous
REVEL	0.03	moderately benign-leaning
SaProt	LLR -5.55	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.43	GERP -0.088, phastCons 0.99
Regional constraint	o/e 0.83	unconstrained · MANE · 8,572 bp · p 0.0022 · regional, not allelic
Overall
CADD	14.79	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 0.00171% Admixed American · 1/58,552 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000687% 10/1,454,832 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00171%	58,552
Finnishnot grpmax-eligible	0.00157%	63,880
European (non-Finnish)	0.000679%	147,193

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: MSMO1
Protein: p.Phe65Leu
Coding: c.195C>A
MANE Select: NM_006745
dbSNP: rs1172820720
Type: single nucleotide variant
Location: chr4:165333565 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.13

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

Similar variants

MSMO1 p.Ala60Gly Uncertain significance ★★ ⚠ same type
MSMO1 p.Asn236Ser Uncertain significance ★★ ⚠ same type
MSMO1 p.Gly273Glu Uncertain significance ★★ same type
MSMO1 p.His105Gln Uncertain significance ★★ ⚠ same type
MSMO1 p.Ile56Met Uncertain significance ★★ ⚠ same type
MSMO1 p.Phe137Leu Uncertain significance ★★ ⚠ same type
MSMO1 p.Trp135Cys Uncertain significance ★★ ⚠ same type
MSMO1 p.Trp52Cys 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-phe65leu (accessed [today's date]).

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