Is MOS p.Ser324= (c.972C>T) pathogenic?

MOS p.Ser324= (c.972C>T) is classified Likely benign in MOS (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-01). Rare (popmax 0.323%, nfe).

How common is MOS p.Ser324= (c.972C>T) in the general population?

MOS p.Ser324= (c.972C>T) is rare (popmax 0.323%, nfe) (gnomAD).

MOS p.Ser324=

c.972C>T · rs140662288 · VCV1879712

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.323%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2	GERP -3.7
Overall
CADD	2.107	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.323% European (non-Finnish) · 3,767/1,165,842 alleles

Filtering AF 0.314% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.311%

Overall 0.289% 4,569/1,583,210 alleles · rare exomes 4,211/1,430,866 · genomes 358/152,344 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.822%	122
European (non-Finnish)grpmax	0.323%	309
Remaining individualsnot grpmax-eligible	0.244%	409
Admixed American	0.14%	713
Middle Eastern	0.101%	987
African / African-American	0.0544%	1,838
Ashkenazi Jewishnot grpmax-eligible	0.0466%	2,148

Finnish 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: MOS
Protein: p.Ser324=
Coding: c.972C>T
MANE Select: NM_005372
dbSNP: rs140662288
Type: single nucleotide variant
Location: chr8:56113011 (GRCh38)
Gene constraint: LOEUF 1.944 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 80.98
Residue 324: the protein kinase domain; a UniProt-annotated variant site (in ozema20; likely pathogenic; loss of function in oocyte maturation activation; loss of activation of the erk1/erk2 cascade; severely decreased interaction with map2k1)

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

Similar variants

MOS p.Ser182Ter Likely pathogenic ★ same type
MOS p.Ala154Thr Uncertain significance ★ ⚠ same type
MOS p.Ala247Val Uncertain significance ★ ⚠ same type
MOS p.Ala277Glu Uncertain significance ★ ⚠ same type
MOS p.Ala289Thr Uncertain significance ★ ⚠ same type
MOS p.Ala292Val Uncertain significance ★ same type
MOS p.Ala43Thr Uncertain significance ★ ⚠ same type
MOS p.Arg12Leu 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/mos-p-ser324 (accessed [today's date]).

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