Is MAPK1 p.Pro319= (c.957G>A) pathogenic?

MAPK1 p.Pro319= (c.957G>A) is classified Likely benign in MAPK1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2021-08-23). Very rare (popmax 0.005%, amr); Associated with MAPK1-related disorder.

What condition is associated with MAPK1 p.Pro319= (c.957G>A)?

MAPK1 p.Pro319= (c.957G>A) is associated with MAPK1-related disorder (ClinVar).

How common is MAPK1 p.Pro319= (c.957G>A) in the general population?

MAPK1 p.Pro319= (c.957G>A) is very rare (popmax 0.005%, amr) (gnomAD).

MAPK1 p.Pro319=

c.957G>A · rs778814312 · VCV3029212

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Conditions

MAPK1-related disorder

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 -4.7	GERP -3.8
Overall
CADD	6.673	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.005% Admixed American · 3/59,998 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000744% 12/1,612,982 alleles · very rare exomes 11/1,460,812 · genomes 1/152,170 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	19,999
South Asian	0.0011%	91,036
European (non-Finnish)	0.000678%	147,387

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: MAPK1
Protein: p.Pro319=
Coding: c.957G>A
MANE Select: NM_002745
dbSNP: rs778814312
Type: single nucleotide variant
Location: chr22:21772882 (GRCh38)
Gene constraint: LOEUF 0.377 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 90.99 · 157 PDB
Residue 319: an α-helix

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

Disease context

MAPK1-related disorder

Similar variants

MAPK1 p.Pro319Leu Uncertain significance ★ same residue
MAPK1 c.725-4A>G Uncertain significance ★ same condition
MAPK1 c.492+10G>A Likely benign same condition
MAPK1 c.610-9C>T Likely benign same condition
MAPK1 p.Thr94Ala Likely benign same condition
MAPK1 p.Ala7_Gly8insAlaAla Uncertain significance ★★ same condition
MAPK1 c.120-20CT[5] Likely benign same condition
MAPK1 p.Ala7del Benign same condition

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-pro319 (accessed [today's date]).

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