Is DAAM2 p.Ser114Arg (c.342T>G) pathogenic?

DAAM2 p.Ser114Arg (c.342T>G) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-07). AlphaMissense: ambiguous (0.5102); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Ser114Arg (c.342T>G)?

DAAM2 p.Ser114Arg (c.342T>G) is associated with Inborn genetic diseases (ClinVar).

How common is DAAM2 p.Ser114Arg (c.342T>G) in the general population?

DAAM2 p.Ser114Arg (c.342T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAAM2 p.Ser114Arg (c.342T>G)?

AlphaMissense predicts ambiguous (score 0.5102) — an in-silico prediction, not a clinical call.

DAAM2 p.Ser114Arg

c.342T>G · VCV3838098

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5102 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5102	ambiguous
REVEL	0.249	benign-leaning
SaProt	LLR -7.52	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.092	GERP -1.8, phastCons 0.81
Regional constraint	o/e 1.04	unconstrained · MANE · 8,771 bp · p 0.57 · regional, not allelic
Overall
CADD	18.31	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.Ser114Arg
Coding: c.342T>G
MANE Select: NM_001201427
Type: single nucleotide variant
Location: chr6:39864988 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 114: 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

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.Glu956Lys 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

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-ser114arg (accessed [today's date]).

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