Is MAPK13 p.Val147Met (c.439G>A) pathogenic?

MAPK13 p.Val147Met (c.439G>A) is classified Uncertain significance in MAPK13 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-20). AlphaMissense: ambiguous (0.5625); Ultra-rare (popmax 0.0165%, mid).

How common is MAPK13 p.Val147Met (c.439G>A) in the general population?

MAPK13 p.Val147Met (c.439G>A) is ultra-rare (popmax 0.0165%, mid) (gnomAD).

What do computational predictors say about MAPK13 p.Val147Met (c.439G>A)?

AlphaMissense predicts ambiguous (score 0.5625) — an in-silico prediction, not a clinical call.

MAPK13 p.Val147Met

c.439G>A · rs544518831 · VCV2380589

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5625 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0165%, mid)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5625	ambiguous
REVEL	0.231	benign-leaning
SaProt	LLR -9.08	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.088
Regional constraint	o/e 0.98	unconstrained · MANE · 8,787 bp · p 0.59 · regional, not allelic
Overall
CADD	19.25	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 0.0165% Middle Eastern · 1/6,060 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00308%

Overall 0.0026% 42/1,614,088 alleles · ultra-rare exomes 36/1,461,858 · genomes 6/152,230 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0165%	6,060
African / African-American	0.00933%	10,717
Remaining individualsnot grpmax-eligible	0.008%	12,501
Admixed American	0.00666%	15,004
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,606
South Asian	0.00329%	30,361
East Asian	0.00223%	44,866
European (non-Finnish)	0.00169%	59,000

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: MAPK13
Protein: p.Val147Met
Coding: c.439G>A
MANE Select: NM_002754
dbSNP: rs544518831
Type: single nucleotide variant
Location: chr6:36136040 (GRCh38)
Gene constraint: LOEUF 0.906 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 89.14 · 8 PDB
Residue 147: the protein kinase domain

Full MAPK13 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAPK13 p.Ala281Gly Uncertain significance ★ ⚠ same type
MAPK13 p.Ala302Thr Uncertain significance ★ ⚠ same type
MAPK13 p.Ala320Ser Uncertain significance ★ ⚠ same type
MAPK13 p.Arg276Trp Uncertain significance ★ ⚠ same type
MAPK13 p.Arg296His Uncertain significance ★ ⚠ same type
MAPK13 p.Arg354Gln Uncertain significance ★ ⚠ same type
MAPK13 p.Arg354Trp Uncertain significance ★ ⚠ same type
MAPK13 p.Arg358Trp 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/mapk13-p-val147met (accessed [today's date]).

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