Is DMAP1 p.Arg283His (c.848G>A) pathogenic?

DMAP1 p.Arg283His (c.848G>A) is classified Uncertain significance in DMAP1 (ClinVar, Multiple submitters, 3 submitters; last evaluated 2024-07-07). AlphaMissense: likely benign (0.3031); Ultra-rare (popmax 0.064%, nfe).

How common is DMAP1 p.Arg283His (c.848G>A) in the general population?

DMAP1 p.Arg283His (c.848G>A) is ultra-rare (popmax 0.064%, nfe) (gnomAD).

What do computational predictors say about DMAP1 p.Arg283His (c.848G>A)?

AlphaMissense predicts likely benign (score 0.3031) — an in-silico prediction, not a clinical call.

DMAP1 p.Arg283His

c.848G>A · rs150290470 · VCV806129

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.3031 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.064%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3031	likely benign
REVEL	0.408	indeterminate
SaProt	LLR -7.34	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.63	unconstrained · MANE · 1,518 bp · p 2.6e-10 · regional, not allelic
Overall
CADD	33.0	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 0.064% European (non-Finnish) · 755/1,180,044 alleles

Filtering AF 0.0602% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0586%

Overall 0.0487% 786/1,614,030 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.064%	1,563
Remaining individualsnot grpmax-eligible	0.0224%	4,463
African / African-American	0.0133%	7,493
Admixed American	0.005%	20,002
East Asian	0.00445%	22,447
Finnishnot grpmax-eligible	0.00312%	32,004

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.Arg283His
Coding: c.848G>A
MANE Select: NM_019100
dbSNP: rs150290470
Type: single nucleotide variant
Location: chr1:44219183 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.46 · 18 PDB
Residue 283: 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.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
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-arg283his (accessed [today's date]).

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