Is MAP3K11 p.Arg73Gln (c.218G>A) pathogenic?

MAP3K11 p.Arg73Gln (c.218G>A) is classified Uncertain significance in MAP3K11 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.0978); Ultra-rare (popmax 0.0213%, nfe).

How common is MAP3K11 p.Arg73Gln (c.218G>A) in the general population?

MAP3K11 p.Arg73Gln (c.218G>A) is ultra-rare (popmax 0.0213%, nfe) (gnomAD).

What do computational predictors say about MAP3K11 p.Arg73Gln (c.218G>A)?

AlphaMissense predicts likely benign (score 0.0978) — an in-silico prediction, not a clinical call.

MAP3K11 p.Arg73Gln

c.218G>A · rs138254027 · VCV2239629

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0978 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0213%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0978	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -5.85	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 4.1	GERP -0.85, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 366 bp · p 0.57 · regional, not allelic
Overall
CADD	24.1	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 0.0213% European (non-Finnish) · 251/1,178,248 alleles

Filtering AF 0.0191% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0183%

Overall 0.017% 273/1,610,572 alleles · ultra-rare exomes 252/1,458,384 · genomes 21/152,188 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0213%	4,694
Remaining individualsnot grpmax-eligible	0.0176%	5,669
Admixed American	0.00835%	11,980
Finnishnot grpmax-eligible	0.00634%	15,761
African / African-American	0.00267%	37,437

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: MAP3K11
Protein: p.Arg73Gln
Coding: c.218G>A
MANE Select: NM_002419
dbSNP: rs138254027
Type: single nucleotide variant
Location: chr11:65613539 (GRCh38)
Gene constraint: LOEUF 0.79 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 63.79 · 4 PDB
Residue 73: the sh3 domain; a β-strand

Full MAP3K11 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP3K11 p.Ala169Thr Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala282Pro Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala287Thr Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala352Ser Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala370Val Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala378Thr Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala39Gly Uncertain significance ★ ⚠ same type
MAP3K11 p.Ala42Ser 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/map3k11-p-arg73gln (accessed [today's date]).

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