Is DMAP1 p.Trp97Cys (c.291G>C) pathogenic?

DMAP1 p.Trp97Cys (c.291G>C) is classified Uncertain significance in DMAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-08-01). AlphaMissense: likely pathogenic (0.9891); Absent from gnomAD v4.1; Associated with intellectual disability.

What condition is associated with DMAP1 p.Trp97Cys (c.291G>C)?

DMAP1 p.Trp97Cys (c.291G>C) is associated with intellectual disability (ClinVar).

How common is DMAP1 p.Trp97Cys (c.291G>C) in the general population?

DMAP1 p.Trp97Cys (c.291G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DMAP1 p.Trp97Cys (c.291G>C)?

AlphaMissense predicts likely pathogenic (score 0.9891) — an in-silico prediction, not a clinical call.

DMAP1 p.Trp97Cys

c.291G>C · rs2154314160 · VCV1679257

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9891 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

intellectual disability

Computational evidence

Protein change
AlphaMissense	0.9891	likely pathogenic
REVEL	0.557	indeterminate
SaProt	LLR -13.67	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	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	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DMAP1
Protein: p.Trp97Cys
Coding: c.291G>C
MANE Select: NM_019100
dbSNP: rs2154314160
Type: single nucleotide variant
Location: chr1:44214796 (GRCh38)
Gene constraint: LOEUF 0.691 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 75.46 · 18 PDB
Residue 97: a β-strand

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

Disease context

intellectual disability — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DMAP1 p.Glu342fs Likely pathogenic ★ same condition
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-trp97cys (accessed [today's date]).

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