MAP4K4 p.Ser736=
c.2208T>C · rs773330069 · VCV3123116
Likely benign
Single submitter
Classification
Likely benign
ClinVar
Review
Single submitter ★☆☆☆
ClinVar · 1 submitter
gnomAD v4.1
Rare
very rare (popmax 0.00382%, nfe)
Conditions
1
Inborn genetic diseases
Computational evidence
| Protein change | ||
| Missense predictors do not apply to this variant type; conservation carries the signal. | ||
| REVEL | 0.067 | moderately benign-leaning |
|---|---|---|
| Splicing | ||
| SpliceAI | — | not assessed · no allele here is in the release |
| Constraint at this position | ||
| Conservation | phyloP 1.9 | GERP -2.2, phastCons 1 |
| Overall | ||
| CADD | 10.13 | PHRED · no single calibrated threshold — expert panels disagree |
Population frequency
gnomAD v4.1 · exomes + genomes
Grpmax group
0.00382%
European (non-Finnish) · 45/1,177,754 alleles
Filtering AF
0.00291%
ClinGen BA1/BS1 input
FAF95, joint · FAF99 0.0026%
Overall
0.00292%
47/1,611,162 alleles · very rare
exomes 44/1,459,120 · genomes 3/152,042 · joint denominator
| Ancestry group | Frequency | 1 in |
|---|---|---|
| European (non-Finnish)grpmax | 0.00382% | 26,172 |
| Remaining individualsnot grpmax-eligible | 0.00321% | 31,159 |
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
- MAP4K4
- Protein
- p.Ser736=
- Coding
- c.2208T>C
- MANE Select
- NM_001395002
- dbSNP
- rs773330069
- Type
- single nucleotide variant
- Location
- chr2:101866431 (GRCh38)
- Gene constraint
- LOEUF 0.308 · pLI 1.00 (gnomAD)
- Structure
- AlphaFold pLDDT 66.47 · 19 PDB
- Residue 736
- the 'disordered' region
Similar variants
- MAP4K4 p.Arg1329Ter Pathogenic/Likely pathogenic ★★ same condition
- MAP4K4 p.Ala491Pro Uncertain significance ★★ ⚠ same condition
- MAP4K4 p.Leu742Pro Uncertain significance ★★ ⚠ same condition
- MAP4K4 p.Ser758Phe Uncertain significance ★★ ⚠ same condition
- MAP4K4 p.Asp203Gly Likely pathogenic ★ same condition
- MAP4K4 p.Gln402Ter Pathogenic ★ same condition
- MAP4K4 p.Gly173Asp Pathogenic ★ same condition
- MAP4K4 p.Lys54Arg Likely pathogenic ★ 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/map4k4-p-ser736 (accessed [today's date]).
Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown