Is DAAM1 p.Val230Met (c.688G>A) pathogenic?

DAAM1 p.Val230Met (c.688G>A) is classified Uncertain significance in DAAM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-08). AlphaMissense: ambiguous (0.4074); Ultra-rare (popmax 0.0134%, eas).

How common is DAAM1 p.Val230Met (c.688G>A) in the general population?

DAAM1 p.Val230Met (c.688G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about DAAM1 p.Val230Met (c.688G>A)?

AlphaMissense predicts ambiguous (score 0.4074) — an in-silico prediction, not a clinical call.

DAAM1 p.Val230Met

c.688G>A · rs564090602 · VCV2514690

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4074 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4074	ambiguous
REVEL	0.68	pathogenic-leaning
SaProt	LLR -10.39	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.9, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 39 kb · p 1.1e-08 · regional, not allelic
Overall
CADD	26.6	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 0.0134% East Asian · 6/44,816 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00525%

Overall 0.00899% 145/1,613,522 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.0656%	1,524
East Asiangrpmax	0.0134%	7,469
African / African-American	0.0107%	9,362
European (non-Finnish)	0.00695%	14,388
Admixed American	0.005%	19,993
Remaining individualsnot grpmax-eligible	0.0032%	31,223
South Asian	0.0022%	45,509

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Val230Met
Coding: c.688G>A
MANE Select: NM_001270520
dbSNP: rs564090602
Type: single nucleotide variant
Location: chr14:59323139 (GRCh38)
Gene constraint: LOEUF 0.509 · pLI 0.54 (gnomAD)
Structure: AlphaFold pLDDT 80.52 · 2 PDB
Residue 230: the gbd/fh3 domain

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-val230met (accessed [today's date]).

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