Is MAP3K7 p.Arg372Cys (c.1114C>T) pathogenic?

MAP3K7 p.Arg372Cys (c.1114C>T) is classified Uncertain significance in MAP3K7 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-27). AlphaMissense: likely benign (0.3345); Very rare (popmax 0.00168%, amr); Associated with Inborn genetic diseases.

What condition is associated with MAP3K7 p.Arg372Cys (c.1114C>T)?

MAP3K7 p.Arg372Cys (c.1114C>T) is associated with Inborn genetic diseases (ClinVar).

How common is MAP3K7 p.Arg372Cys (c.1114C>T) in the general population?

MAP3K7 p.Arg372Cys (c.1114C>T) is very rare (popmax 0.00168%, amr) (gnomAD).

What do computational predictors say about MAP3K7 p.Arg372Cys (c.1114C>T)?

AlphaMissense predicts likely benign (score 0.3345) — an in-silico prediction, not a clinical call.

MAP3K7 p.Arg372Cys

c.1114C>T · rs778131562 · VCV2522364

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3345 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00168%, amr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3345	likely benign
REVEL	0.499	indeterminate
SaProt	LLR -9.74	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 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 33 kb · p 0.12 · regional, not allelic
Overall
CADD	29.0	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 0.00168% Admixed American · 1/59,562 alleles

Filtering AF 0.000501% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000366%

Overall 0.00093% 15/1,612,230 alleles · very rare exomes 15/1,460,052 · genomes 0/152,178 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,556
Remaining individualsnot grpmax-eligible	0.00321%	31,195
Admixed Americangrpmax	0.00168%	59,562
European (non-Finnish)	0.000933%	107,210

Ashkenazi Jewish 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: MAP3K7
Protein: p.Arg372Cys
Coding: c.1114C>T
MANE Select: NM_145331
dbSNP: rs778131562
Type: single nucleotide variant
Location: chr6:90547354 (GRCh38)
Gene constraint: LOEUF 0.397 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.27 · 25 PDB
Residue 372: the 'disordered' region

Full MAP3K7 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

MAP3K7 p.Arg372His Uncertain significance ★ ⚠ same residue
MAP3K7 p.Ala313Thr Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Ala400Thr Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Ala6Thr Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Arg289Gln Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Arg347His Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Asn342Asp Uncertain significance ★★ ⚠ same condition
MAP3K7 p.Gly411Asp Uncertain significance ★★ ⚠ 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/map3k7-p-arg372cys (accessed [today's date]).

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