Is DAPL1 p.Ala22Val (c.65C>T) pathogenic?

DAPL1 p.Ala22Val (c.65C>T) is classified Uncertain significance in DAPL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-13). AlphaMissense: likely benign (0.2048); Very rare (popmax 0.00017%, nfe).

How common is DAPL1 p.Ala22Val (c.65C>T) in the general population?

DAPL1 p.Ala22Val (c.65C>T) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about DAPL1 p.Ala22Val (c.65C>T)?

AlphaMissense predicts likely benign (score 0.2048) — an in-silico prediction, not a clinical call.

DAPL1 p.Ala22Val

c.65C>T · rs1271732197 · VCV2559909

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2048 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.2048	likely benign
REVEL	0.355	indeterminate
SaProt	LLR -4.59	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.7, phastCons 1
Regional constraint	o/e 1.25	unconstrained · MANE · 20 kb · p 0.0052 · regional, not allelic
Overall
CADD	25.5	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 0.00017% European (non-Finnish) · 2/1,175,504 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000124% 2/1,606,748 alleles · very rare exomes 1/1,454,656 · genomes 1/152,092 · joint denominator

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.Ala22Val
Coding: c.65C>T
MANE Select: NM_001017920
dbSNP: rs1271732197
Type: single nucleotide variant
Location: chr2:158804288 (GRCh38)
Gene constraint: LOEUF 1.834 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 68.31
Residue 22: the 'disordered' region

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

Similar variants

DAPL1 p.Ala19Pro 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-ala22val (accessed [today's date]).

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