Is DAAM2 p.Arg172His (c.515G>A) pathogenic?

DAAM2 p.Arg172His (c.515G>A) is classified Benign in DAAM2 (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-07-30). AlphaMissense: likely benign (0.127); Rare (popmax 0.347%, nfe); Associated with DAAM2-related disorder.

What condition is associated with DAAM2 p.Arg172His (c.515G>A)?

DAAM2 p.Arg172His (c.515G>A) is associated with DAAM2-related disorder (ClinVar).

How common is DAAM2 p.Arg172His (c.515G>A) in the general population?

DAAM2 p.Arg172His (c.515G>A) is rare (popmax 0.347%, nfe) (gnomAD).

What do computational predictors say about DAAM2 p.Arg172His (c.515G>A)?

AlphaMissense predicts likely benign (score 0.127) — an in-silico prediction, not a clinical call.

DAAM2 p.Arg172His

c.515G>A · rs200589550 · VCV3039245

Benign No assertion criteria

Classification

Benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.127 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.347%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

DAAM2-related disorder

Computational evidence

Protein change
AlphaMissense	0.127	likely benign
REVEL	0.574	indeterminate
SaProt	LLR -5.46	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.7	GERP 2.4, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 11 kb · p 5e-07 · regional, not allelic
Overall
CADD	29.6	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 0.347% European (non-Finnish) · 4,100/1,179,888 alleles

Filtering AF 0.339% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.335%

Overall 0.301% 4,856/1,613,992 alleles · rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.18%	85
Remaining individualsnot grpmax-eligible	0.368%	272
European (non-Finnish)grpmax	0.347%	288
Admixed American	0.207%	484
African / African-American	0.0426%	2,345
Middle Eastern	0.033%	3,031
Finnishnot grpmax-eligible	0.025%	4,002
East Asian	0.00446%	22,444
South Asian	0.0022%	45,537

Ashkenazi Jewish 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.Arg172His
Coding: c.515G>A
MANE Select: NM_001201427
dbSNP: rs200589550
Type: single nucleotide variant
Location: chr6:39867596 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 172: the gbd/fh3 domain

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

Disease context

DAAM2-related disorder

Similar variants

DAAM2 p.Arg172Cys Uncertain significance ★ ⚠ same residue
DAAM2 p.Ala829Thr Uncertain significance ⚠ same condition
DAAM2 p.Glu997Lys Uncertain significance ⚠ same condition
DAAM2 p.Gly527Val Uncertain significance ⚠ same condition
DAAM2 c.1845+7A>G Likely benign same condition
DAAM2 c.2342-10C>T Likely benign same condition
DAAM2 c.2983-4G>A Likely benign same condition
DAAM2 c.2983-8G>C Likely 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/daam2-p-arg172his (accessed [today's date]).

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