Is DMAP1 p.Arg452Gln (c.1355G>A) pathogenic?

DMAP1 p.Arg452Gln (c.1355G>A) is classified Uncertain significance in DMAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-14). AlphaMissense: likely pathogenic (0.8586); Very rare (popmax 0.00659%, sas).

How common is DMAP1 p.Arg452Gln (c.1355G>A) in the general population?

DMAP1 p.Arg452Gln (c.1355G>A) is very rare (popmax 0.00659%, sas) (gnomAD).

What do computational predictors say about DMAP1 p.Arg452Gln (c.1355G>A)?

AlphaMissense predicts likely pathogenic (score 0.8586) — an in-silico prediction, not a clinical call.

DMAP1 p.Arg452Gln

c.1355G>A · VCV4241291

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8586 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00659%, sas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8586	likely pathogenic
REVEL	0.255	benign-leaning
SaProt	LLR -8.02	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 1,518 bp · p 2.6e-10 · regional, not allelic
Overall
CADD	27.6	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 0.00659% South Asian · 6/91,090 alleles

Filtering AF 0.00286% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00195%

Overall 0.00118% 19/1,614,110 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00659%	15,182
European (non-Finnish)	0.0011%	90,772

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.Arg452Gln
Coding: c.1355G>A
MANE Select: NM_019100
Type: single nucleotide variant
Location: chr1:44220569 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.46 · 18 PDB
Residue 452: 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.Ala2Thr 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-arg452gln (accessed [today's date]).

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