Is MAP2K3 p.Arg55Thr (c.164G>C) pathogenic?

MAP2K3 p.Arg55Thr (c.164G>C) is classified Benign in MAP2K3 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-06-04). AlphaMissense: likely benign (0.1221); Common (popmax 50%, amr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about MAP2K3 p.Arg55Thr (c.164G>C)?

AlphaMissense predicts likely benign (score 0.1221) — an in-silico prediction, not a clinical call.

MAP2K3 p.Arg55Thr

Q: How common is MAP2K3 p.Arg55Thr (c.164G>C) in the general population?

MAP2K3 p.Arg55Thr (c.164G>C) is common (popmax 50%, amr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.164G>C · rs36047035 · VCV768843

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1221 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 50%, amr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1221	likely benign
REVEL	0.109	moderately benign-leaning
SaProt	LLR -7.04	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 6.2	GERP 0.96, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 20 kb · p 0.26 · regional, not allelic
Overall
CADD	24.6	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 50% Admixed American · 30,002/60,006 alleles

Filtering AF 49.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 49.8%

Overall 50% 805,281/1,610,942 alleles · common exomes 729,109/1,458,578 · genomes 76,172/152,364 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	50%	2
Amishnot grpmax-eligible	50%	2
Admixed Americangrpmax	50%	2
East Asian	50%	2
South Asian	50%	2
Ashkenazi Jewishnot grpmax-eligible	50%	2
Remaining individualsnot grpmax-eligible	50%	2
African / African-American	50%	2
European (non-Finnish)	50%	2
Middle Eastern	50%	2

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: MAP2K3
Protein: p.Arg55Thr
Coding: c.164G>C
MANE Select: NM_145109
dbSNP: rs36047035
Type: single nucleotide variant
Location: chr17:21298925 (GRCh38)
Gene constraint: LOEUF 0.993 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.13
Residue 55: a UniProt-annotated variant site (in)

Full MAP2K3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP2K3 p.Leu215Trp Uncertain significance ★★ ⚠ same type
MAP2K3 c.568+10C>T Benign ★★ same type
MAP2K3 p.Ala220= Benign ★★ same type
MAP2K3 p.Ala225= Likely benign ★★ same type
MAP2K3 p.Leu25= Benign ★★ same type
MAP2K3 p.Leu319= Likely benign ★★ same type
MAP2K3 p.Pro40Thr Benign ★★ same type
MAP2K3 p.Ser286= 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/map2k3-p-arg55thr (accessed [today's date]).

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