Is DAAM1 p.Pro959Ala (c.2875C>G) pathogenic?

DAAM1 p.Pro959Ala (c.2875C>G) is classified Uncertain significance in DAAM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-16). AlphaMissense: ambiguous (0.4358); Absent from gnomAD v4.1.

How common is DAAM1 p.Pro959Ala (c.2875C>G) in the general population?

DAAM1 p.Pro959Ala (c.2875C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAAM1 p.Pro959Ala (c.2875C>G)?

AlphaMissense predicts ambiguous (score 0.4358) — an in-silico prediction, not a clinical call.

DAAM1 p.Pro959Ala

c.2875C>G · rs2503305507 · VCV2278930

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4358 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4358	ambiguous
REVEL	0.497	indeterminate
SaProt	LLR -9.11	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 38 kb · p 0.049 · regional, not allelic
Overall
CADD	26.2	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P969A vs ClinVar P959A) — verify the residue.

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: DAAM1
Protein: p.Pro959Ala
Coding: c.2875C>G
MANE Select: NM_001270520
dbSNP: rs2503305507
Type: single nucleotide variant
Location: chr14:59367477 (GRCh38)
Gene constraint: LOEUF 0.509 · pLI 0.54 (gnomAD)
Structure: AlphaFold pLDDT 80.52 · 2 PDB
Residue 959: the fh2 domain; an α-helix

Full DAAM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAAM1 p.Arg1011Gly Uncertain significance ★★ same type
DAAM1 p.Phe752Leu Uncertain significance ★★ ⚠ same type
DAAM1 p.Asn865His Benign ★★ same type
DAAM1 p.Asp679= Likely benign ★★ same type
DAAM1 p.Leu804= Benign ★★ same type
DAAM1 p.Pro49= Benign ★★ same type
DAAM1 c.1969-1685T>C Uncertain significance ★ ⚠ same type
DAAM1 c.1969-1686T>G 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/daam1-p-pro959ala (accessed [today's date]).

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