Is MAP2K5 p.Arg436Trp (c.1306C>T) pathogenic?

MAP2K5 p.Arg436Trp (c.1306C>T) is classified Uncertain significance in MAP2K5 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-20). AlphaMissense: ambiguous (0.407); Very rare (popmax 0.00243%, eas).

How common is MAP2K5 p.Arg436Trp (c.1306C>T) in the general population?

MAP2K5 p.Arg436Trp (c.1306C>T) is very rare (popmax 0.00243%, eas) (gnomAD).

What do computational predictors say about MAP2K5 p.Arg436Trp (c.1306C>T)?

AlphaMissense predicts ambiguous (score 0.407) — an in-silico prediction, not a clinical call.

MAP2K5 p.Arg436Trp

c.1306C>T · rs762647820 · VCV3122783

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.407 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00243%, eas)

Computational evidence

Protein change
AlphaMissense	0.407	ambiguous
REVEL	0.555	indeterminate
SaProt	LLR -10.95	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.95	GERP -4.7, phastCons 0.99
Regional constraint	o/e 1.08	unconstrained · MANE · 100 bp · p 0.57 · regional, not allelic
Overall
CADD	24.0	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 0.00243% East Asian · 1/41,096 alleles

Filtering AF 0.0003% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000217%

Overall 0.000709% 11/1,551,984 alleles · very rare exomes 8/1,399,752 · genomes 3/152,232 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00243%	41,096
Remaining individualsnot grpmax-eligible	0.00166%	60,182
South Asian	0.00119%	84,182
European (non-Finnish)	0.000697%	143,503

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: MAP2K5
Protein: p.Arg436Trp
Coding: c.1306C>T
MANE Select: NM_145160
dbSNP: rs762647820
Type: single nucleotide variant
Location: chr15:67806709 (GRCh38)
Gene constraint: LOEUF 1.201 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.20 · 3 PDB

Full MAP2K5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP2K5 p.Arg436Gln Uncertain significance ★ ⚠ same residue
MAP2K5 p.Arg436Leu Uncertain significance ★ same residue
MAP2K5 c.586-8A>G Benign ★★ same type
MAP2K5 c.1074+1G>A Uncertain significance ★ same type
MAP2K5 p.Ala150Ser Uncertain significance ★ ⚠ same type
MAP2K5 p.Ala157Thr Uncertain significance ★ ⚠ same type
MAP2K5 p.Ala266Val Uncertain significance ★ ⚠ same type
MAP2K5 p.Ala437Ser 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/map2k5-p-arg436trp (accessed [today's date]).

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