Is DCTPP1 p.Ile8Phe (c.22A>T) pathogenic?

DCTPP1 p.Ile8Phe (c.22A>T) is classified Uncertain significance in DCTPP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-18). AlphaMissense: likely benign (0.0876); Ultra-rare (popmax 0.0308%, amr).

How common is DCTPP1 p.Ile8Phe (c.22A>T) in the general population?

DCTPP1 p.Ile8Phe (c.22A>T) is ultra-rare (popmax 0.0308%, amr) (gnomAD).

What do computational predictors say about DCTPP1 p.Ile8Phe (c.22A>T)?

AlphaMissense predicts likely benign (score 0.0876) — an in-silico prediction, not a clinical call.

DCTPP1 p.Ile8Phe

c.22A>T · rs773060140 · VCV2379804

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0876 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0308%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0876	likely benign
REVEL	0.03	moderately benign-leaning
SaProt	LLR -7.34	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 -3.7	GERP -3.5
Regional constraint	o/e 1.00	unconstrained · MANE · 5,744 bp · p 0.97 · regional, not allelic
Overall
CADD	0.175	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 0.0308% Admixed American · 17/55,260 alleles

Filtering AF 0.0196% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.016%

Overall 0.00197% 31/1,576,402 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0308%	3,251
Remaining individualsnot grpmax-eligible	0.00822%	12,162
Ashkenazi Jewishnot grpmax-eligible	0.00703%	14,229
European (non-Finnish)	0.000602%	166,137

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: DCTPP1
Protein: p.Ile8Phe
Coding: c.22A>T
MANE Select: NM_024096
dbSNP: rs773060140
Type: single nucleotide variant
Location: chr16:30429959 (GRCh38)
Gene constraint: LOEUF 1.458 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.40 · 5 PDB
Residue 8: the 'disordered' region

Full DCTPP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DCTPP1 p.Ala18Pro Uncertain significance ★ ⚠ same type
DCTPP1 p.Arg109Cys Uncertain significance ★ ⚠ same type
DCTPP1 p.Arg111Cys Uncertain significance ★ ⚠ same type
DCTPP1 p.Arg126Trp Uncertain significance ★ ⚠ same type
DCTPP1 p.Arg135Cys Uncertain significance ★ ⚠ same type
DCTPP1 p.Arg135His Uncertain significance ★ ⚠ same type
DCTPP1 p.Arg22Trp Uncertain significance ★ ⚠ same type
DCTPP1 p.Arg35Cys 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/dctpp1-p-ile8phe (accessed [today's date]).

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