Is DAAM1 p.Ala452Val (c.1355C>T) pathogenic?

DAAM1 p.Ala452Val (c.1355C>T) is classified Uncertain significance in DAAM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-26). AlphaMissense: likely pathogenic (0.9413); Ultra-rare (popmax 0.012%, afr).

How common is DAAM1 p.Ala452Val (c.1355C>T) in the general population?

DAAM1 p.Ala452Val (c.1355C>T) is ultra-rare (popmax 0.012%, afr) (gnomAD).

What do computational predictors say about DAAM1 p.Ala452Val (c.1355C>T)?

AlphaMissense predicts likely pathogenic (score 0.9413) — an in-silico prediction, not a clinical call.

DAAM1 p.Ala452Val

c.1355C>T · VCV3499470

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9413 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.012%, afr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.9413	likely pathogenic
REVEL	0.309	indeterminate
SaProt	LLR -5.97	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
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 0.75	unconstrained · MANE · 39 kb · p 1.1e-08 · regional, not allelic
Overall
CADD	26.7	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 0.012% African / African-American · 9/74,922 alleles

Filtering AF 0.00623% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00468%

Overall 0.00186% 30/1,613,616 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.012%	8,325
South Asian	0.00549%	18,212
Admixed American	0.00167%	59,976
Remaining individualsnot grpmax-eligible	0.0016%	62,496
European (non-Finnish)	0.00119%	84,274

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: DAAM1
Protein: p.Ala452Val
Coding: c.1355C>T
MANE Select: NM_001270520
Type: single nucleotide variant
Location: chr14:59326974 (GRCh38)
Gene constraint: LOEUF 0.509 · pLI 0.54 (gnomAD)
Structure: AlphaFold pLDDT 80.52 · 2 PDB

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

Similar variants

DAAM1 p.Ala452Thr Uncertain significance ★ ⚠ same residue
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

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-ala452val (accessed [today's date]).

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