Is DAAM2 p.Pro198Ser (c.592C>T) pathogenic?

DAAM2 p.Pro198Ser (c.592C>T) is classified Uncertain significance in DAAM2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.1245); Rare (popmax 0.164%, afr); Associated with Inborn genetic diseases.

What condition is associated with DAAM2 p.Pro198Ser (c.592C>T)?

DAAM2 p.Pro198Ser (c.592C>T) is associated with Inborn genetic diseases (ClinVar).

How common is DAAM2 p.Pro198Ser (c.592C>T) in the general population?

DAAM2 p.Pro198Ser (c.592C>T) is rare (popmax 0.164%, afr) (gnomAD).

What do computational predictors say about DAAM2 p.Pro198Ser (c.592C>T)?

AlphaMissense predicts likely benign (score 0.1245) — an in-silico prediction, not a clinical call.

DAAM2 p.Pro198Ser

c.592C>T · rs115708591 · VCV2386126

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1245 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.164%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.1245	likely benign
REVEL	0.524	indeterminate
SaProt	LLR -6.87	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 4	GERP 0.38, phastCons 1
Regional constraint	o/e 0.76	unconstrained · MANE · 11 kb · p 5e-07 · regional, not allelic
Overall
CADD	24.9	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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 0.164% African / African-American · 123/75,060 alleles

Filtering AF 0.14% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.131%

Overall 0.00892% 144/1,614,038 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.164%	610
Middle Eastern	0.033%	3,031
Remaining individualsnot grpmax-eligible	0.0176%	5,681
South Asian	0.00549%	18,217
Admixed American	0.005%	20,010

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.Pro198Ser
Coding: c.592C>T
MANE Select: NM_001201427
dbSNP: rs115708591
Type: single nucleotide variant
Location: chr6:39867673 (GRCh38)
Gene constraint: LOEUF 0.488 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 80.02
Residue 198: the gbd/fh3 domain

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

Similar variants

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DAAM2 p.Arg990Cys Uncertain significance ★★ ⚠ same condition
DAAM2 p.Gln760Arg Uncertain significance ★★ ⚠ same condition
DAAM2 p.Glu956Lys Uncertain significance ★★ ⚠ same condition
DAAM2 p.Ile699Val Uncertain significance ★★ ⚠ same condition
DAAM2 p.Ala117Val Uncertain significance ★ ⚠ same condition
DAAM2 p.Ala167Thr Uncertain significance ★ ⚠ 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-pro198ser (accessed [today's date]).

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