Is DAAM1 p.Pro556= (c.1668T>A) pathogenic?

DAAM1 p.Pro556= (c.1668T>A) is classified Likely benign in DAAM1 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-10-29). Low-frequency (popmax 1.28%, eas); Associated with DAAM1-related disorder.

What condition is associated with DAAM1 p.Pro556= (c.1668T>A)?

DAAM1 p.Pro556= (c.1668T>A) is associated with DAAM1-related disorder (ClinVar).

How common is DAAM1 p.Pro556= (c.1668T>A) in the general population?

DAAM1 p.Pro556= (c.1668T>A) is low-frequency (popmax 1.28%, eas) (gnomAD).

DAAM1 p.Pro556=

c.1668T>A · rs781426332 · VCV3038460

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.28%, eas)

Conditions

DAAM1-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · T>C here scores Δ0.20 · evaluated, not missing
Constraint at this position
Conservation	phyloP -0.26	GERP -2.4
Overall
CADD	1.468	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.28% East Asian · 231/17,994 alleles

Filtering AF 1.15% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1%

Overall 0.256% 2,771/1,083,420 alleles · low-frequency

Ancestry group	Frequency	1 in
East Asiangrpmax	1.28%	78
Ashkenazi Jewishnot grpmax-eligible	0.749%	134
Remaining individualsnot grpmax-eligible	0.465%	215
Middle Eastern	0.455%	220
Finnishnot grpmax-eligible	0.437%	229
Admixed American	0.35%	286
African / African-American	0.325%	308
Amishnot grpmax-eligible	0.222%	450
European (non-Finnish)	0.214%	468
South Asian	0.0735%	1,360

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.Pro556=
Coding: c.1668T>A
MANE Select: NM_001270520
dbSNP: rs781426332
Type: single nucleotide variant
Location: chr14:59331316 (GRCh38)
Gene constraint: LOEUF 0.509 · pLI 0.54 (gnomAD)
Structure: AlphaFold pLDDT 80.52 · 2 PDB
Residue 556: the fh1 domain; the 'disordered' region

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

Disease context

DAAM1-related disorder

Similar variants

DAAM1 p.Gly964Asp Uncertain significance ★ ⚠ same condition
DAAM1 c.1373-6G>A Benign same condition
DAAM1 c.2694+8T>C Likely benign same condition
DAAM1 p.Ala509= Benign same condition
DAAM1 p.Gln463= Benign same condition
DAAM1 p.Gly8= Likely benign same condition
DAAM1 p.Leu241= Benign same condition
DAAM1 p.Lys186= Benign 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/daam1-p-pro556 (accessed [today's date]).

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