Is DMAP1 p.Val241Met (c.721G>A) pathogenic?

DMAP1 p.Val241Met (c.721G>A) is classified Uncertain significance in DMAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-03). AlphaMissense: ambiguous (0.4531); Very rare (popmax 0.000254%, nfe).

How common is DMAP1 p.Val241Met (c.721G>A) in the general population?

DMAP1 p.Val241Met (c.721G>A) is very rare (popmax 0.000254%, nfe) (gnomAD).

What do computational predictors say about DMAP1 p.Val241Met (c.721G>A)?

AlphaMissense predicts ambiguous (score 0.4531) — an in-silico prediction, not a clinical call.

DMAP1 p.Val241Met

c.721G>A · VCV3502510

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4531 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000254%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4531	ambiguous
REVEL	0.213	benign-leaning
SaProt	LLR -8.62	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 1.8, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 740 bp · p 0.54 · regional, not allelic
Overall
CADD	33.0	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 0.000254% European (non-Finnish) · 3/1,179,910 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.00118% 19/1,613,734 alleles · very rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0235%	4,264
Remaining individualsnot grpmax-eligible	0.0016%	62,466
European (non-Finnish)grpmax	0.000254%	393,303

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val241Met
Coding: c.721G>A
MANE Select: NM_019100
Type: single nucleotide variant
Location: chr1:44219056 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.46 · 18 PDB
Residue 241: an α-helix

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

Similar variants

DMAP1 p.Val241Ala Uncertain significance ★ ⚠ same residue
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

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-val241met (accessed [today's date]).

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