Is MAP2K5 p.Arg169Gln (c.506G>A) pathogenic?

MAP2K5 p.Arg169Gln (c.506G>A) is classified Uncertain significance in MAP2K5 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-12-23). AlphaMissense: likely benign (0.0718); Very rare (popmax 0.00541%, afr).

How common is MAP2K5 p.Arg169Gln (c.506G>A) in the general population?

MAP2K5 p.Arg169Gln (c.506G>A) is very rare (popmax 0.00541%, afr) (gnomAD).

What do computational predictors say about MAP2K5 p.Arg169Gln (c.506G>A)?

AlphaMissense predicts likely benign (score 0.0718) — an in-silico prediction, not a clinical call.

MAP2K5 p.Arg169Gln

c.506G>A · VCV3870103

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0718 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00541%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0718	likely benign
REVEL	0.058	moderately benign-leaning
SaProt	LLR -3.09	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.6	GERP 0.44, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 103 kb · p 0.54 · regional, not allelic
Overall
CADD	19.89	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.00541% African / African-American · 4/73,996 alleles

Filtering AF 0.00224% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00199%

Overall 0.00274% 44/1,608,614 alleles · very rare exomes 41/1,457,060 · genomes 3/151,554 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00541%	18,499
Remaining individualsnot grpmax-eligible	0.00321%	31,113
European (non-Finnish)	0.00305%	32,735
South Asian	0.00221%	45,191

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.Arg169Gln
Coding: c.506G>A
MANE Select: NM_145160
Type: single nucleotide variant
Location: chr15:67600710 (GRCh38)
Gene constraint: LOEUF 1.201 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.20 · 3 PDB
Residue 169: the protein kinase domain

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

Similar variants

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
MAP2K5 p.Arg125Gln Uncertain significance ★ ⚠ same type
MAP2K5 p.Arg125Trp 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-arg169gln (accessed [today's date]).

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