Is MAP4 p.Ile1813Lys (c.5438T>A) pathogenic?

MAP4 p.Ile1813Lys (c.5438T>A) is classified Uncertain significance in MAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-14). AlphaMissense: likely benign (0.2306); Ultra-rare (popmax 0.0625%, eas).

How common is MAP4 p.Ile1813Lys (c.5438T>A) in the general population?

MAP4 p.Ile1813Lys (c.5438T>A) is ultra-rare (popmax 0.0625%, eas) (gnomAD).

What do computational predictors say about MAP4 p.Ile1813Lys (c.5438T>A)?

AlphaMissense predicts likely benign (score 0.2306) — an in-silico prediction, not a clinical call.

MAP4 p.Ile1813Lys

c.5438T>A · rs143298732 · VCV2516578

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2306 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0625%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2306	likely benign
REVEL	0.145	moderately benign-leaning
SaProt	LLR -5.48	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>C here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 2.2	GERP -0.98, phastCons 0.91
Regional constraint	o/e 0.91	unconstrained · MANE · 123 kb · p 2.5e-05 · regional, not allelic
Overall
CADD	19.03	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

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

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM I668K vs ClinVar I1813K) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0625% East Asian · 28/44,822 alleles

Filtering AF 0.0443% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0383%

Overall 0.00479% 77/1,608,278 alleles · ultra-rare exomes 66/1,456,022 · genomes 11/152,256 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0625%	1,601
Remaining individualsnot grpmax-eligible	0.00642%	15,572
European (non-Finnish)	0.00349%	28,665
African / African-American	0.00267%	37,431
Admixed American	0.00167%	59,740
South Asian	0.0011%	90,816

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.Ile1813Lys
Coding: c.5438T>A
MANE Select: NM_001385682
dbSNP: rs143298732
Type: single nucleotide variant
Location: chr3:47877520 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03
Residue 668 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-ile1813lys (accessed [today's date]).

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