Is MOS p.Cys320Phe (c.959G>T) pathogenic?

MOS p.Cys320Phe (c.959G>T) is classified Uncertain significance in MOS (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-14). AlphaMissense: likely pathogenic (0.6321); Very rare (popmax 0.000257%, nfe).

How common is MOS p.Cys320Phe (c.959G>T) in the general population?

MOS p.Cys320Phe (c.959G>T) is very rare (popmax 0.000257%, nfe) (gnomAD).

What do computational predictors say about MOS p.Cys320Phe (c.959G>T)?

AlphaMissense predicts likely pathogenic (score 0.6321) — an in-silico prediction, not a clinical call.

MOS p.Cys320Phe

c.959G>T · VCV3295614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6321 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000257%, nfe)

Missense predictors

3/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6321	likely pathogenic
REVEL	0.915	moderately pathogenic-leaning
SaProt	LLR -15.37	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 4	GERP 0.95, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 1,037 bp · p 0.058 · regional, not allelic
Overall
CADD	27.3	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

Grpmax group 0.000257% European (non-Finnish) · 3/1,168,754 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000189% 3/1,589,566 alleles · very rare exomes 3/1,437,206 · genomes 0/152,360 · joint denominator

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.Cys320Phe
Coding: c.959G>T
MANE Select: NM_005372
Type: single nucleotide variant
Location: chr8:56113024 (GRCh38)
Gene constraint: LOEUF 1.944 · pLI 0.10 (gnomAD)
Structure: AlphaFold pLDDT 80.98
Residue 320: 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.Cys320Ter Pathogenic same residue
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

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-cys320phe (accessed [today's date]).

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