Is DAPL1 p.Ala19Pro (c.55G>C) pathogenic?

DAPL1 p.Ala19Pro (c.55G>C) is classified Uncertain significance in DAPL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-25). AlphaMissense: likely pathogenic (0.6467); Rare (popmax 0.226%, eas).

How common is DAPL1 p.Ala19Pro (c.55G>C) in the general population?

DAPL1 p.Ala19Pro (c.55G>C) is rare (popmax 0.226%, eas) (gnomAD).

What do computational predictors say about DAPL1 p.Ala19Pro (c.55G>C)?

AlphaMissense predicts likely pathogenic (score 0.6467) — an in-silico prediction, not a clinical call.

DAPL1 p.Ala19Pro

c.55G>C · VCV4658474

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6467 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.226%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.6467	likely pathogenic · top 7% in DAPL1
REVEL	0.503	indeterminate
SaProt	LLR -5.64	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 20 kb · p 0.0052 · regional, not allelic
Overall
CADD	26.9	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 0.226% East Asian · 93/41,202 alleles

Filtering AF 0.189% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.175%

Overall 0.00605% 94/1,554,690 alleles · rare exomes 86/1,402,354 · genomes 8/152,336 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.226%	443
Remaining individualsnot grpmax-eligible	0.00166%	60,310

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: DAPL1
Protein: p.Ala19Pro
Coding: c.55G>C
MANE Select: NM_001017920
Type: single nucleotide variant
Location: chr2:158795427 (GRCh38)
Gene constraint: LOEUF 1.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.31
Residue 19: the 'disordered' region

Full DAPL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DAPL1 p.Ala22Val Uncertain significance ★ ⚠ same type
DAPL1 p.Ala2Glu Uncertain significance ★ ⚠ same type
DAPL1 p.Ala50Val Uncertain significance ★ ⚠ same type
DAPL1 p.Ala62Asp Uncertain significance ★ ⚠ same type
DAPL1 p.Ala62Thr Uncertain significance ★ ⚠ same type
DAPL1 p.Ala66Glu Uncertain significance ★ ⚠ same type
DAPL1 p.Arg105Gln Uncertain significance ★ ⚠ same type
DAPL1 p.Arg12Gln Uncertain significance ★ ⚠ 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/dapl1-p-ala19pro (accessed [today's date]).

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