Is MAP4K1 p.Arg236Ter (c.706C>T) pathogenic?

MAP4K1 p.Arg236Ter (c.706C>T) is classified Uncertain significance in MAP4K1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-25). Very rare (popmax 0.0011%, sas).

How common is MAP4K1 p.Arg236Ter (c.706C>T) in the general population?

MAP4K1 p.Arg236Ter (c.706C>T) is very rare (popmax 0.0011%, sas) (gnomAD).

MAP4K1 p.Arg236Ter

c.706C>T · VCV4942204

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

Consequence

nonsense (stop-gain)

predicted LoF

gnomAD v4.1

Rare

very rare (popmax 0.0011%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	nonsense (stop-gain)	predicted loss-of-function in a LoF-intolerant gene
NMD	predicted	premature termination codon in exon 10 of 31
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -4.9, phastCons 1
Overall
CADD	38.0	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0011% South Asian · 1/91,040 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000205% 3/1,461,384 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0011%	91,040
European (non-Finnish)	0.00017%	589,797

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: MAP4K1
Protein: p.Arg236Ter
Coding: c.706C>T
MANE Select: NM_001042600
Type: single nucleotide variant
Location: chr19:38611265 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 68.83 · 50 PDB
Residue 236: the protein kinase domain

Full MAP4K1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP4K1 p.Ala246Ser Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala313Pro Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala452Ser Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala452Thr Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala452Val Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala485Ser Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala609Val Uncertain significance ★ ⚠ same type
MAP4K1 p.Ala661Gly 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/map4k1-p-arg236ter (accessed [today's date]).

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