Is DAAM2 p.Glu956Lys (c.2866G>A) pathogenic?

DAAM2 p.Glu956Lys (c.2866G>A) is classified Uncertain significance in DAAM2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-03-08). AlphaMissense: likely pathogenic (0.6348); Ultra-rare (popmax 0.0329%, mid); Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Glu956Lys (c.2866G>A)?

DAAM2 p.Glu956Lys (c.2866G>A) is associated with Inborn genetic diseases (ClinVar).

How common is DAAM2 p.Glu956Lys (c.2866G>A) in the general population?

DAAM2 p.Glu956Lys (c.2866G>A) is ultra-rare (popmax 0.0329%, mid) (gnomAD).

What do computational predictors say about DAAM2 p.Glu956Lys (c.2866G>A)?

AlphaMissense predicts likely pathogenic (score 0.6348) — an in-silico prediction, not a clinical call.

DAAM2 p.Glu956Lys

c.2866G>A · rs370518716 · VCV2230233

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6348 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0329%, mid)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6348	likely pathogenic
REVEL	0.266	benign-leaning
SaProt	LLR -9.61	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 9.9	GERP 2.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.46 · regional, not allelic
Overall
CADD	29.5	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 0.0329% Middle Eastern · 2/6,084 alleles

Filtering AF 0.0213% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0205%

Overall 0.0194% 313/1,613,826 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0329%	3,042
European (non-Finnish)	0.0236%	4,229
Remaining individualsnot grpmax-eligible	0.0224%	4,462
South Asian	0.00988%	10,120
African / African-American	0.00534%	18,726
Admixed American	0.005%	20,001
Finnishnot grpmax-eligible	0.00312%	32,003

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: DAAM2
Protein: p.Glu956Lys
Coding: c.2866G>A
MANE Select: NM_001201427
dbSNP: rs370518716
Type: single nucleotide variant
Location: chr6:39901356 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 956: a UniProt-annotated variant site (in nphs24; affects the regulation of filopodia formation); the fh2 domain

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

DAAM2 p.Arg335Trp Uncertain significance ★★ ⚠ same condition
DAAM2 p.Arg676Trp Uncertain significance ★★ ⚠ same condition
DAAM2 p.Arg990Cys Uncertain significance ★★ ⚠ same condition
DAAM2 p.Gln760Arg Uncertain significance ★★ ⚠ same condition
DAAM2 p.Ile699Val Uncertain significance ★★ ⚠ same condition
DAAM2 p.Ala117Val Uncertain significance ★ ⚠ same condition
DAAM2 p.Ala167Thr Uncertain significance ★ ⚠ same condition
DAAM2 p.Ala247Val Uncertain significance ★ ⚠ 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-glu956lys (accessed [today's date]).

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