Is DAAM1 p.Pro566Gln (c.1697C>A) pathogenic?

DAAM1 p.Pro566Gln (c.1697C>A) is classified Uncertain significance in DAAM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-07-10). AlphaMissense: likely benign (0.2672); Very rare (popmax 0.00017%, nfe).

How common is DAAM1 p.Pro566Gln (c.1697C>A) in the general population?

DAAM1 p.Pro566Gln (c.1697C>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about DAAM1 p.Pro566Gln (c.1697C>A)?

AlphaMissense predicts likely benign (score 0.2672) — an in-silico prediction, not a clinical call.

DAAM1 p.Pro566Gln

c.1697C>A · rs373008354 · VCV2610160

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2672 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.2672	likely benign
REVEL	0.503	indeterminate
SaProt	LLR -13.97	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.9, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 38 kb · p 0.049 · regional, not allelic
Overall
CADD	23.4	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 0.00017% European (non-Finnish) · 2/1,179,442 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000137% 2/1,459,900 alleles · very rare

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.Pro566Gln
Coding: c.1697C>A
MANE Select: NM_001270520
dbSNP: rs373008354
Type: single nucleotide variant
Location: chr14:59331345 (GRCh38)
Gene constraint: LOEUF 0.509 · pLI 0.54 (gnomAD)
Structure: AlphaFold pLDDT 80.52 · 2 PDB
Residue 566: the fh1 domain; the 'disordered' region

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-pro566gln (accessed [today's date]).

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