Is MAP4 p.Asp2220Asn (c.6658G>A) pathogenic?

MAP4 p.Asp2220Asn (c.6658G>A) is classified Uncertain significance in MAP4 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-12). AlphaMissense: likely pathogenic (0.9257); Rare (popmax 0.149%, mid).

How common is MAP4 p.Asp2220Asn (c.6658G>A) in the general population?

MAP4 p.Asp2220Asn (c.6658G>A) is rare (popmax 0.149%, mid) (gnomAD).

What do computational predictors say about MAP4 p.Asp2220Asn (c.6658G>A)?

AlphaMissense predicts likely pathogenic (score 0.9257) — an in-silico prediction, not a clinical call.

MAP4 p.Asp2220Asn

c.6658G>A · rs139009148 · VCV2309206

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9257 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.149%, mid)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9257	likely pathogenic · top 5% in MAP4
REVEL	0.669	pathogenic-leaning
SaProt	LLR -9.61	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 2.4, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 23 kb · p 0.28 · regional, not allelic
Overall
CADD	31.0	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 D1075N vs ClinVar D2220N) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.149% Middle Eastern · 9/6,060 alleles

Filtering AF 0.0774% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0578%

Overall 0.00124% 20/1,614,064 alleles · rare exomes 17/1,461,822 · genomes 3/152,242 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.149%	673
African / African-American	0.00267%	37,511
Admixed American	0.00167%	60,016
Remaining individualsnot grpmax-eligible	0.0016%	62,506
European (non-Finnish)	0.000593%	168,568

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.Asp2220Asn
Coding: c.6658G>A
MANE Select: NM_001385682
dbSNP: rs139009148
Type: single nucleotide variant
Location: chr3:47855286 (GRCh38)
Gene constraint: LOEUF 0.512 · pLI 0.14 (gnomAD)
Structure: AlphaFold pLDDT 43.03
Residue 1075 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-asp2220asn (accessed [today's date]).

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