Is DAP3 p.Cys395Ser (c.1183T>A) pathogenic?

DAP3 p.Cys395Ser (c.1183T>A) is classified Uncertain significance in DAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-23). AlphaMissense: likely benign (0.3173); Ultra-rare (popmax 0.0386%, afr).

How common is DAP3 p.Cys395Ser (c.1183T>A) in the general population?

DAP3 p.Cys395Ser (c.1183T>A) is ultra-rare (popmax 0.0386%, afr) (gnomAD).

What do computational predictors say about DAP3 p.Cys395Ser (c.1183T>A)?

AlphaMissense predicts likely benign (score 0.3173) — an in-silico prediction, not a clinical call.

DAP3 p.Cys395Ser

c.1183T>A · rs111463064 · VCV2455367

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.3173 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0386%, afr)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.3173	likely benign
REVEL	0.301	indeterminate
SaProt	LLR -8.20	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 7.8	GERP 2.1, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 28 kb · p 0.25 · regional, not allelic
Overall
CADD	21.2	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 0.0386% African / African-American · 29/75,074 alleles

Filtering AF 0.0276% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0238%

Overall 0.00291% 47/1,614,234 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0386%	2,589
Remaining individualsnot grpmax-eligible	0.0224%	4,465
Middle Eastern	0.0165%	6,062
Admixed American	0.00333%	30,013
South Asian	0.0011%	91,086

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.Cys395Ser
Coding: c.1183T>A
MANE Select: NM_004632
dbSNP: rs111463064
Type: single nucleotide variant
Location: chr1:155738228 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.23 · 86 PDB
Residue 395: a UniProt-annotated variant site (in prlts7; likely pathogenic; decreased thermal stability; decreased gtpase activity); an α-helix

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

Similar variants

DAP3 p.Cys395Tyr Pathogenic/Likely pathogenic 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-cys395ser (accessed [today's date]).

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