Is MAP3K1 p.Phe327Cys (c.980T>G) pathogenic?

MAP3K1 p.Phe327Cys (c.980T>G) is classified Uncertain significance in MAP3K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely pathogenic (0.997); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with MAP3K1 p.Phe327Cys (c.980T>G)?

MAP3K1 p.Phe327Cys (c.980T>G) is associated with Inborn genetic diseases (ClinVar).

How common is MAP3K1 p.Phe327Cys (c.980T>G) in the general population?

MAP3K1 p.Phe327Cys (c.980T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about MAP3K1 p.Phe327Cys (c.980T>G)?

AlphaMissense predicts likely pathogenic (score 0.997) — an in-silico prediction, not a clinical call.

MAP3K1 p.Phe327Cys

c.980T>G · VCV4624258

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.997 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.997	likely pathogenic · top 4% in MAP3K1
REVEL	0.729	pathogenic-leaning
SaProt	LLR -9.77	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.7, phastCons 1
Regional constraint	o/e 0.27	constrained · MANE · 507 bp · p 3.3e-06 · regional, not allelic
Overall
CADD	28.5	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: MAP3K1
Protein: p.Phe327Cys
Coding: c.980T>G
MANE Select: NM_005921
Type: single nucleotide variant
Location: chr5:56864879 (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

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

Similar variants

MAP3K1 p.Ala594Ser Uncertain significance ★★ ⚠ same condition
MAP3K1 p.Arg204Lys Uncertain significance ★★ ⚠ same condition
MAP3K1 p.Val1346Ile Uncertain significance ★★ ⚠ same condition
MAP3K1 p.Pro962= Benign/Likely benign ★★ same condition
MAP3K1 p.Leu189Gln Likely pathogenic ★ ⚠ same condition
MAP3K1 p.Ala1017Val Uncertain significance ★ ⚠ same condition
MAP3K1 p.Ala1327Pro Uncertain significance ★ ⚠ same condition
MAP3K1 p.Ala1402Gly 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/map3k1-p-phe327cys (accessed [today's date]).

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