Is DAP3 p.Arg197Cys (c.589C>T) pathogenic?

DAP3 p.Arg197Cys (c.589C>T) is classified Uncertain significance in DAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-08). AlphaMissense: likely benign (0.082); Ultra-rare (popmax 0.02%, nfe).

How common is DAP3 p.Arg197Cys (c.589C>T) in the general population?

DAP3 p.Arg197Cys (c.589C>T) is ultra-rare (popmax 0.02%, nfe) (gnomAD).

What do computational predictors say about DAP3 p.Arg197Cys (c.589C>T)?

AlphaMissense predicts likely benign (score 0.082) — an in-silico prediction, not a clinical call.

DAP3 p.Arg197Cys

c.589C>T · rs150553683 · VCV2348894

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.082 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.02%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.082	likely benign
REVEL	0.231	benign-leaning
SaProt	LLR -11.43	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.6	GERP -0.15, phastCons 0.027
Regional constraint	o/e 0.95	unconstrained · MANE · 28 kb · p 0.25 · regional, not allelic
Overall
CADD	24.6	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 0.02% European (non-Finnish) · 236/1,179,496 alleles

Filtering AF 0.0179% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0171%

Overall 0.0215% 346/1,612,984 alleles · ultra-rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.142%	703
Remaining individualsnot grpmax-eligible	0.0256%	3,902
European (non-Finnish)grpmax	0.02%	4,998
African / African-American	0.00267%	37,421
South Asian	0.0011%	90,960

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: DAP3
Protein: p.Arg197Cys
Coding: c.589C>T
MANE Select: NM_004632
dbSNP: rs150553683
Type: single nucleotide variant
Location: chr1:155727724 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.23 · 86 PDB
Residue 197: a turn

Full DAP3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAP3 p.Arg197His Uncertain significance ★ ⚠ same residue
YY1AP1 c.-151-185G>A Uncertain significance ★★ same type
DAP3 p.Arg20Cys Likely benign ★★ ⚠ same type
DAP3 p.Val240Phe Benign ★★ same type
YY1AP1 c.-151-68T>C Benign/Likely benign ★★ same type
YY1AP1 c.-30C>T Benign ★★ same type
YY1AP1 c.-49T>C Benign ★★ same type
YY1AP1 c.-60T>C Benign/Likely benign ★★ 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/dap3-p-arg197cys (accessed [today's date]).

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