Is DAAM2 p.Ala117Val (c.350C>T) pathogenic?

DAAM2 p.Ala117Val (c.350C>T) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.0882); Ultra-rare (popmax 0.0187%, amr); Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Ala117Val (c.350C>T)?

DAAM2 p.Ala117Val (c.350C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DAAM2 p.Ala117Val (c.350C>T) in the general population?

DAAM2 p.Ala117Val (c.350C>T) is ultra-rare (popmax 0.0187%, amr) (gnomAD).

What do computational predictors say about DAAM2 p.Ala117Val (c.350C>T)?

AlphaMissense predicts likely benign (score 0.0882) — an in-silico prediction, not a clinical call.

DAAM2 p.Ala117Val

c.350C>T · VCV4237293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0882 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0187%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0882	likely benign
REVEL	0.106	moderately benign-leaning
SaProt	LLR -6.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2	GERP 0.11, phastCons 0.56
Regional constraint	o/e 1.04	unconstrained · MANE · 8,771 bp · p 0.57 · regional, not allelic
Overall
CADD	17.52	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 0.0187% Admixed American · 11/58,940 alleles

Filtering AF 0.0104% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00808%

Overall 0.00206% 33/1,605,442 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0187%	5,358
Remaining individualsnot grpmax-eligible	0.00321%	31,125
European (non-Finnish)	0.0017%	58,817

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.Ala117Val
Coding: c.350C>T
MANE Select: NM_001201427
Type: single nucleotide variant
Location: chr6:39864996 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 117: the gbd/fh3 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

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DAAM2 p.Gln760Arg Uncertain significance ★★ ⚠ same condition
DAAM2 p.Glu956Lys Uncertain significance ★★ ⚠ same condition
DAAM2 p.Ile699Val 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-ala117val (accessed [today's date]).

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