Is DAAM2 p.Glu997Lys (c.2989G>A) pathogenic?

DAAM2 p.Glu997Lys (c.2989G>A) is classified Uncertain significance in DAAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2024-04-15). AlphaMissense: ambiguous (0.5401); Absent from gnomAD v4.1; Associated with DAAM2-related disorder.

What condition is associated with DAAM2 p.Glu997Lys (c.2989G>A)?

DAAM2 p.Glu997Lys (c.2989G>A) is associated with DAAM2-related disorder (ClinVar).

How common is DAAM2 p.Glu997Lys (c.2989G>A) in the general population?

DAAM2 p.Glu997Lys (c.2989G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAAM2 p.Glu997Lys (c.2989G>A)?

AlphaMissense predicts ambiguous (score 0.5401) — an in-silico prediction, not a clinical call.

DAAM2 p.Glu997Lys

c.2989G>A · VCV3345919

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5401 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

DAAM2-related disorder

Computational evidence

Protein change
AlphaMissense	0.5401	ambiguous
REVEL	0.374	indeterminate
SaProt	LLR -10.40	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.46 · regional, not allelic
Overall
CADD	25.1	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

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: DAAM2
Protein: p.Glu997Lys
Coding: c.2989G>A
MANE Select: NM_001201427
Type: single nucleotide variant
Location: chr6:39901819 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 997: a UniProt-annotated variant site (in nphs24; affects the regulation of filopodia formation)

Full DAAM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

DAAM2-related disorder

Similar variants

DAAM2 p.Ala829Thr Uncertain significance ⚠ same condition
DAAM2 p.Gly527Val Uncertain significance ⚠ same condition
DAAM2 c.1845+7A>G Likely benign same condition
DAAM2 c.2342-10C>T Likely benign same condition
DAAM2 c.2983-4G>A Likely benign same condition
DAAM2 c.2983-8G>C Likely benign same condition
DAAM2 p.Ala1054Thr Likely benign same condition
DAAM2 p.Ala869= Benign same condition

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/daam2-p-glu997lys (accessed [today's date]).

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