Is DMAP1 p.Ala2Thr (c.4G>A) pathogenic?

DMAP1 p.Ala2Thr (c.4G>A) is classified Uncertain significance in DMAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-28). AlphaMissense: likely benign (0.2029); Very rare (popmax 0.00723%, nfe).

How common is DMAP1 p.Ala2Thr (c.4G>A) in the general population?

DMAP1 p.Ala2Thr (c.4G>A) is very rare (popmax 0.00723%, nfe) (gnomAD).

What do computational predictors say about DMAP1 p.Ala2Thr (c.4G>A)?

AlphaMissense predicts likely benign (score 0.2029) — an in-silico prediction, not a clinical call.

DMAP1 p.Ala2Thr

c.4G>A · rs374557407 · VCV3083010

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2029 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00723%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2029	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -8.14	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 0.62	unconstrained · MANE · 4,601 bp · p 1.9e-07 · regional, not allelic
Overall
CADD	23.1	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.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00723% European (non-Finnish) · 84/1,162,458 alleles

Filtering AF 0.00596% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00549%

Overall 0.00558% 88/1,578,008 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00723%	13,839
Remaining individualsnot grpmax-eligible	0.00327%	30,602
Admixed American	0.00182%	54,872
South Asian	0.00117%	85,798

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: DMAP1
Protein: p.Ala2Thr
Coding: c.4G>A
MANE Select: NM_019100
dbSNP: rs374557407
Type: single nucleotide variant
Location: chr1:44213757 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.46 · 18 PDB
Residue 2: the 'disordered' region

Full DMAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DMAP1 p.Arg224Ter Uncertain significance ★★ same type
DMAP1 p.Arg283His Uncertain significance ★★ ⚠ same type
DMAP1 p.Tyr196Ser Uncertain significance ★★ ⚠ same type
DMAP1 p.Arg226Trp Likely pathogenic ★ same type
DMAP1 c.1344+3A>G Uncertain significance ★ same type
DMAP1 c.394-1G>C Uncertain significance ★ same type
DMAP1 p.Ala207Thr Uncertain significance ★ ⚠ same type
DMAP1 p.Ala411Pro 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/dmap1-p-ala2thr (accessed [today's date]).

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