Is MAPK1 p.Ser320Ile (c.959G>T) pathogenic?

MAPK1 p.Ser320Ile (c.959G>T) is classified Uncertain significance in MAPK1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-28). AlphaMissense: likely benign (0.3122); Absent from gnomAD v4.1.

How common is MAPK1 p.Ser320Ile (c.959G>T) in the general population?

MAPK1 p.Ser320Ile (c.959G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAPK1 p.Ser320Ile (c.959G>T)?

AlphaMissense predicts likely benign (score 0.3122) — an in-silico prediction, not a clinical call.

MAPK1 p.Ser320Ile

c.959G>T · rs2148633839 · VCV1695839

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3122 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.3122	likely benign
REVEL	0.184	benign-leaning
SaProt	LLR -11.23	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 0.91, phastCons 1
Regional constraint	o/e 0.45	unconstrained · MANE · 19 kb · p 1.4e-10 · regional, not allelic
Overall
CADD	25.4	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

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: MAPK1
Protein: p.Ser320Ile
Coding: c.959G>T
MANE Select: NM_002745
dbSNP: rs2148633839
Type: single nucleotide variant
Location: chr22:21772880 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 157 PDB
Residue 320: an α-helix

Full MAPK1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK1 p.Ala174Val Pathogenic ★★ ⚠ same type
MAPK1 p.Arg135Thr Likely pathogenic ★★ same type
MAPK1 p.Asp318Asn Pathogenic/Likely pathogenic ★★ same type
MAPK1 p.Asp318Gly Pathogenic ★★ same type
MAPK1 p.Glu322Gln Pathogenic/Likely pathogenic ★★ same type
MAPK1 p.His80Tyr Pathogenic ★★ same type
MAPK1 p.Asn27Asp Uncertain significance ★★ ⚠ same type
MAPK1 p.Ala325= Likely benign ★★ 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/mapk1-p-ser320ile (accessed [today's date]).

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