Is MAP3K6 p.Pro958Thr (c.2872C>A) pathogenic?

MAP3K6 p.Pro958Thr (c.2872C>A) is classified Likely benign in MAP3K6 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2020-11-02). AlphaMissense: likely benign (0.0688); Low-frequency (popmax 1.15%, eas); Associated with MAP3K6-related disorder.

What condition is associated with MAP3K6 p.Pro958Thr (c.2872C>A)?

MAP3K6 p.Pro958Thr (c.2872C>A) is associated with MAP3K6-related disorder (ClinVar).

How common is MAP3K6 p.Pro958Thr (c.2872C>A) in the general population?

MAP3K6 p.Pro958Thr (c.2872C>A) is low-frequency (popmax 1.15%, eas) (gnomAD).

What do computational predictors say about MAP3K6 p.Pro958Thr (c.2872C>A)?

AlphaMissense predicts likely benign (score 0.0688) — an in-silico prediction, not a clinical call.

MAP3K6 p.Pro958Thr

c.2872C>A · rs75893867 · VCV3031754

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0688 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.15%, eas)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

MAP3K6-related disorder

Computational evidence

Protein change
AlphaMissense	0.0688	likely benign
REVEL	0.464	indeterminate
SaProt	LLR -7.40	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3	GERP 0.52, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 11 kb · p 0.00042 · regional, not allelic
Overall
CADD	20.6	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 1.15% East Asian · 512/44,656 alleles

Filtering AF 1.06% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.03%

Overall 0.0327% 523/1,598,500 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.15%	87
Remaining individualsnot grpmax-eligible	0.0178%	5,624

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: MAP3K6
Protein: p.Pro958Thr
Coding: c.2872C>A
MANE Select: NM_004672
dbSNP: rs75893867
Type: single nucleotide variant
Location: chr1:27358224 (GRCh38)
Gene constraint: LOEUF 0.855 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.36
Residue 958: the 'disordered' region

Full MAP3K6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

MAP3K6-related disorder

Similar variants

MAP3K6 c.1415+9C>T Likely benign same condition
MAP3K6 c.2584-6C>T Benign same condition
MAP3K6 c.3259-10C>T Benign same condition
MAP3K6 c.3711+7C>T Likely benign same condition
MAP3K6 p.Ala106= Likely benign same condition
MAP3K6 p.Ala1061Thr Likely benign same condition
MAP3K6 p.Arg668Gly Benign ⚠ same condition
MAP3K6 p.Arg913His 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/map3k6-p-pro958thr (accessed [today's date]).

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