Is MAP4 p.Lys2113Asn (c.6339G>C) pathogenic?

MAP4 p.Lys2113Asn (c.6339G>C) is classified Uncertain significance in MAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-15). AlphaMissense: ambiguous (0.5074); Very rare (popmax 0.000339%, nfe).

How common is MAP4 p.Lys2113Asn (c.6339G>C) in the general population?

MAP4 p.Lys2113Asn (c.6339G>C) is very rare (popmax 0.000339%, nfe) (gnomAD).

What do computational predictors say about MAP4 p.Lys2113Asn (c.6339G>C)?

AlphaMissense predicts ambiguous (score 0.5074) — an in-silico prediction, not a clinical call.

MAP4 p.Lys2113Asn

c.6339G>C · VCV3293108

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5074 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000339%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.5074	ambiguous
REVEL	0.068	moderately benign-leaning
SaProt	LLR -9.97	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.079	GERP -3, phastCons 0.062
Regional constraint	o/e 0.95	unconstrained · MANE · 23 kb · p 0.28 · regional, not allelic
Overall
CADD	17.83	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM K968N vs ClinVar K2113N) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000339% European (non-Finnish) · 4/1,180,030 alleles

Filtering AF 7.9e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 5.4e-05%

Overall 0.000248% 4/1,614,028 alleles · very rare exomes 3/1,461,874 · genomes 1/152,154 · joint denominator

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.Lys2113Asn
Coding: c.6339G>C
MANE Select: NM_001385682
Type: single nucleotide variant
Location: chr3:47869283 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03
Residue 968 UniProt numbering: 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-lys2113asn (accessed [today's date]).

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