Is DAP3 p.Pro221Ser (c.661C>T) pathogenic?

DAP3 p.Pro221Ser (c.661C>T) is classified Uncertain significance in DAP3 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-15). AlphaMissense: likely benign (0.0911); Absent from gnomAD v4.1.

How common is DAP3 p.Pro221Ser (c.661C>T) in the general population?

DAP3 p.Pro221Ser (c.661C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about DAP3 p.Pro221Ser (c.661C>T)?

AlphaMissense predicts likely benign (score 0.0911) — an in-silico prediction, not a clinical call.

DAP3 p.Pro221Ser

c.661C>T · rs2526486685 · VCV2546261

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0911 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0911	likely benign
REVEL	0.092	moderately benign-leaning
SaProt	LLR -6.47	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 2.6	GERP 1, phastCons 0.75
Regional constraint	o/e 0.95	unconstrained · MANE · 28 kb · p 0.25 · regional, not allelic
Overall
CADD	20.9	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: DAP3
Protein: p.Pro221Ser
Coding: c.661C>T
MANE Select: NM_004632
dbSNP: rs2526486685
Type: single nucleotide variant
Location: chr1:155729099 (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

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
YY1AP1 c.-95G>A 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-pro221ser (accessed [today's date]).

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