Is DAAM2 p.Pro573Leu (c.1718C>T) pathogenic?

DAAM2 p.Pro573Leu (c.1718C>T) is classified Benign in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-03-07). AlphaMissense: likely benign (0.0999); Low-frequency (popmax 1.68%, sas).

How common is DAAM2 p.Pro573Leu (c.1718C>T) in the general population?

DAAM2 p.Pro573Leu (c.1718C>T) is low-frequency (popmax 1.68%, sas) (gnomAD).

What do computational predictors say about DAAM2 p.Pro573Leu (c.1718C>T)?

AlphaMissense predicts likely benign (score 0.0999) — an in-silico prediction, not a clinical call.

DAAM2 p.Pro573Leu

c.1718C>T · rs199956358 · VCV773939

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0999 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.68%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0999	likely benign
REVEL	0.272	benign-leaning
SaProt	LLR -7.41	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 2.5, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.46 · regional, not allelic
Overall
CADD	24.5	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 1.68% South Asian · 1,525/90,824 alleles

Filtering AF 1.61% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.58%

Overall 0.145% 2,333/1,611,702 alleles · low-frequency

Ancestry group	Frequency	1 in
South Asiangrpmax	1.68%	60
East Asian	0.767%	130
Remaining individualsnot grpmax-eligible	0.435%	230
Middle Eastern	0.215%	465
Admixed American	0.0936%	1,069
African / African-American	0.0507%	1,973
European (non-Finnish)	0.00721%	13,865
Ashkenazi Jewishnot grpmax-eligible	0.00339%	29,468

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: DAAM2
Protein: p.Pro573Leu
Coding: c.1718C>T
MANE Select: NM_001201427
dbSNP: rs199956358
Type: single nucleotide variant
Location: chr6:39879350 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 573: a UniProt-annotated variant site (in nphs24; affects the regulation of filopodia formation); the fh1 domain; the 'disordered' region

Full DAAM2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAAM2 p.Pro573Ser Uncertain significance ★ ⚠ same residue
DAAM2 p.Arg335Trp Uncertain significance ★★ ⚠ same type
DAAM2 p.Arg676Trp Uncertain significance ★★ ⚠ same type
DAAM2 p.Arg990Cys Uncertain significance ★★ ⚠ same type
DAAM2 p.Gln760Arg Uncertain significance ★★ ⚠ same type
DAAM2 p.Glu956Lys Uncertain significance ★★ ⚠ same type
DAAM2 p.Ile699Val Uncertain significance ★★ ⚠ same type
DAAM2 p.Pro74Thr 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/daam2-p-pro573leu (accessed [today's date]).

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