Is DAAM2 p.Arg814Cys (c.2440C>T) pathogenic?

DAAM2 p.Arg814Cys (c.2440C>T) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely pathogenic (0.9603); Ultra-rare (popmax 0.0359%, nfe); Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Arg814Cys (c.2440C>T)?

DAAM2 p.Arg814Cys (c.2440C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DAAM2 p.Arg814Cys (c.2440C>T) in the general population?

DAAM2 p.Arg814Cys (c.2440C>T) is ultra-rare (popmax 0.0359%, nfe) (gnomAD).

What do computational predictors say about DAAM2 p.Arg814Cys (c.2440C>T)?

AlphaMissense predicts likely pathogenic (score 0.9603) — an in-silico prediction, not a clinical call.

DAAM2 p.Arg814Cys

c.2440C>T · VCV4237292

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9603 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0359%, nfe)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9603	likely pathogenic
REVEL	0.454	indeterminate
SaProt	LLR -12.05	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 7.6	GERP 0.66, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 24 kb · p 0.46 · regional, not allelic
Overall
CADD	33.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0359% European (non-Finnish) · 424/1,179,782 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.032%

Overall 0.0307% 495/1,613,722 alleles · ultra-rare

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0368%	2,716
European (non-Finnish)grpmax	0.0359%	2,783
Finnishnot grpmax-eligible	0.0297%	3,368
Admixed American	0.0283%	3,529
Middle Eastern	0.0165%	6,054
African / African-American	0.0133%	7,500
East Asian	0.00223%	44,870

Remaining individuals 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: DAAM2
Protein: p.Arg814Cys
Coding: c.2440C>T
Type: single nucleotide variant
Location: chr6:39896910 (GRCh38)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

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-arg814cys (accessed [today's date]).

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