Is MAP4 p.Lys400Glu (c.1198A>G) pathogenic?

MAP4 p.Lys400Glu (c.1198A>G) is classified Uncertain significance in MAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-24). AlphaMissense: likely benign (0.0684); Very rare (popmax 0.00329%, sas).

How common is MAP4 p.Lys400Glu (c.1198A>G) in the general population?

MAP4 p.Lys400Glu (c.1198A>G) is very rare (popmax 0.00329%, sas) (gnomAD).

What do computational predictors say about MAP4 p.Lys400Glu (c.1198A>G)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

MAP4 p.Lys400Glu

c.1198A>G · VCV4103501

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -10.39	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.78	GERP -2.2, phastCons 0.004
Regional constraint	o/e 0.91	unconstrained · MANE · 123 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	10.64	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 0.00329% South Asian · 3/91,084 alleles

Filtering AF 0.0013% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00108%

Overall 0.0018% 29/1,614,134 alleles · very rare exomes 27/1,461,866 · genomes 2/152,268 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,361
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.00195%	51,306
Admixed American	0.00167%	60,008

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: MAP4
Protein: p.Lys400Glu
Coding: c.1198A>G
MANE Select: NM_001385682
Type: single nucleotide variant
Location: chr3:47916629 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03
Residue 400: the '17 x 14 aa tandem repeats' region; the 'disordered' region

Full MAP4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

MAP4 c.292+9T>G Benign ★★ same type
MAP4 p.Gln1950= Benign ★★ same type
MAP4 p.Leu516= Likely benign ★★ same type
MAP4 p.Val37= Benign ★★ same type
MAP4 p.Ala150Ser Uncertain significance ★ ⚠ same type
MAP4 p.Ala1922Val Uncertain significance ★ ⚠ same type
MAP4 p.Ala1926Pro Uncertain significance ★ ⚠ same type
MAP4 p.Ala1941Thr 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/map4-p-lys400glu (accessed [today's date]).

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