Is MSMO1 p.Val204Met (c.610G>A) pathogenic?

MSMO1 p.Val204Met (c.610G>A) is classified Likely benign in MSMO1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2026-01-16). AlphaMissense: likely benign (0.0747); Rare (popmax 0.333%, nfe).

How common is MSMO1 p.Val204Met (c.610G>A) in the general population?

MSMO1 p.Val204Met (c.610G>A) is rare (popmax 0.333%, nfe) (gnomAD).

What do computational predictors say about MSMO1 p.Val204Met (c.610G>A)?

AlphaMissense predicts likely benign (score 0.0747) — an in-silico prediction, not a clinical call.

MSMO1 p.Val204Met

c.610G>A · rs142496142 · VCV731275

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.0747 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.333%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0747	likely benign
REVEL	0.298	indeterminate
SaProt	LLR -5.44	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -7.1	GERP -3.8
Regional constraint	o/e 0.83	unconstrained · MANE · 8,572 bp · p 0.0022 · regional, not allelic
Overall
CADD	0.013	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 0.333% European (non-Finnish) · 3,934/1,179,818 alleles

Filtering AF 0.325% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.321%

Overall 0.283% 4,559/1,613,800 alleles · rare exomes 4,261/1,461,524 · genomes 298/152,276 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.845%	118
European (non-Finnish)grpmax	0.333%	300
Remaining individualsnot grpmax-eligible	0.277%	361
Admixed American	0.0966%	1,035
African / African-American	0.072%	1,389
South Asian	0.0626%	1,598
Finnishnot grpmax-eligible	0.0297%	3,366
East Asian	0.029%	3,450
Middle Eastern	0.0165%	6,058

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val204Met
Coding: c.610G>A
MANE Select: NM_006745
dbSNP: rs142496142
Type: single nucleotide variant
Location: chr4:165340299 (GRCh38)
Gene constraint: LOEUF 0.901 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.13
Residue 204: the fatty acid hydroxylase domain

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-val204met (accessed [today's date]).

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