Is MAP3K1 p.Gln548= (c.1644A>G) pathogenic?

MAP3K1 p.Gln548= (c.1644A>G) is classified Benign in MAP3K1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-26). Common (popmax 7.29%, afr) — too common for a highly-penetrant pathogenic allele; Associated with 46,XY sex reversal 6.

What condition is associated with MAP3K1 p.Gln548= (c.1644A>G)?

MAP3K1 p.Gln548= (c.1644A>G) is associated with 46,XY sex reversal 6 (ClinVar).

MAP3K1 p.Gln548=

Q: How common is MAP3K1 p.Gln548= (c.1644A>G) in the general population?

MAP3K1 p.Gln548= (c.1644A>G) is common (popmax 7.29%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1644A>G · rs56225368 · VCV707219

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.29%, afr) — too common for a highly-penetrant pathogenic allele

Conditions

46,XY sex reversal 6

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1	GERP -2.2, phastCons 1
Overall
CADD	5.745	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.29% African / African-American · 5,469/75,050 alleles

Filtering AF 7.13% ClinGen BA1/BS1 input FAF95, joint · FAF99 7.06%

Overall 0.373% 6,018/1,614,096 alleles · common

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.29%	14
Remaining individualsnot grpmax-eligible	0.418%	239
Admixed American	0.323%	309
Middle Eastern	0.248%	404
South Asian	0.0165%	6,072
Ashkenazi Jewishnot grpmax-eligible	0.00676%	14,802
European (non-Finnish)	0.00525%	19,032

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: MAP3K1
Protein: p.Gln548=
Coding: c.1644A>G
MANE Select: NM_005921
dbSNP: rs56225368
Type: single nucleotide variant
Location: chr5:56872963 (GRCh38)
Gene constraint: LOEUF 0.355 · pLI 1.00 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 59.80 · 1 PDB

Full MAP3K1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

46,XY sex reversal 6 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP3K1 p.Gln548Glu Uncertain significance ★★ ⚠ same residue
MAP3K1 p.Arg186Gly Pathogenic/Likely pathogenic ★★ ⚠ same condition
MAP3K1 p.Ala594Ser Uncertain significance ★★ ⚠ same condition
MAP3K1 p.Arg204Lys Uncertain significance ★★ ⚠ same condition
MAP3K1 c.1035+12C>T Likely benign ★★ same condition
MAP3K1 c.1687-46C>G Benign ★★ same condition
MAP3K1 c.2179+16T>G Benign/Likely benign ★★ same condition
MAP3K1 c.3820-11A>G Benign ★★ same condition

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/map3k1-p-gln548 (accessed [today's date]).

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