Is DAP3 p.Pro281Leu (c.842C>T) pathogenic?

DAP3 p.Pro281Leu (c.842C>T) is classified Likely benign in DAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-31). AlphaMissense: likely benign (0.0568); Ultra-rare (popmax 0.0101%, amr).

How common is DAP3 p.Pro281Leu (c.842C>T) in the general population?

DAP3 p.Pro281Leu (c.842C>T) is ultra-rare (popmax 0.0101%, amr) (gnomAD).

What do computational predictors say about DAP3 p.Pro281Leu (c.842C>T)?

AlphaMissense predicts likely benign (score 0.0568) — an in-silico prediction, not a clinical call.

DAP3 p.Pro281Leu

c.842C>T · VCV3499652

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0568 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0101%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0568	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -7.31	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -4.5	GERP -4.5
Regional constraint	o/e 0.95	unconstrained · MANE · 28 kb · p 0.25 · regional, not allelic
Overall
CADD	1.704	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 0.0101% Admixed American · 6/59,614 alleles

Filtering AF 0.00431% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00297%

Overall 0.00298% 48/1,612,838 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0101%	9,936
African / African-American	0.00535%	18,693
Remaining individualsnot grpmax-eligible	0.00321%	31,195
European (non-Finnish)	0.00288%	34,697
South Asian	0.0022%	45,494

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.Pro281Leu
Coding: c.842C>T
MANE Select: NM_004632
Type: single nucleotide variant
Location: chr1:155729365 (GRCh38)
Gene constraint: LOEUF 0.706 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.23 · 86 PDB

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

Similar variants

DAP3 p.Pro281Arg 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-pro281leu (accessed [today's date]).

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