Is CDIPT p.Ala48Thr (c.142G>A) pathogenic?

CDIPT p.Ala48Thr (c.142G>A) is classified Uncertain significance in CDIPT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-01-07). AlphaMissense: ambiguous (0.5625); Very rare (popmax 8.52e-05%, nfe).

How common is CDIPT p.Ala48Thr (c.142G>A) in the general population?

CDIPT p.Ala48Thr (c.142G>A) is very rare (popmax 8.52e-05%, nfe) (gnomAD).

What do computational predictors say about CDIPT p.Ala48Thr (c.142G>A)?

AlphaMissense predicts ambiguous (score 0.5625) — an in-silico prediction, not a clinical call.

CDIPT p.Ala48Thr

c.142G>A · rs2543392709 · VCV2270763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5625 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.52e-05%, nfe)

Computational evidence

Protein change
AlphaMissense	0.5625	ambiguous
REVEL	0.355	indeterminate
SaProt	LLR -9.45	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.9	GERP 1.6, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 3,665 bp · p 0.068 · regional, not allelic
Overall
CADD	29.6	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 8.52e-05% European (non-Finnish) · 1/1,174,304 alleles

Overall 6.9e-05% 1/1,449,884 alleles · very rare

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: CDIPT
Protein: p.Ala48Thr
Coding: c.142G>A
MANE Select: NM_006319
dbSNP: rs2543392709
Type: single nucleotide variant
Location: chr16:29862622 (GRCh38)
Gene constraint: LOEUF 1.042 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.02

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

Similar variants

CDIPT p.Ala140Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala146Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala206Val Uncertain significance ★ ⚠ same type
CDIPT p.Ala22Ser Uncertain significance ★ ⚠ same type
CDIPT p.Ala84Val Uncertain significance ★ ⚠ same type
CDIPT p.Arg115Gln Uncertain significance ★ ⚠ same type
CDIPT p.Arg138Lys Uncertain significance ★ ⚠ same type
CDIPT p.Arg173Trp 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/cdipt-p-ala48thr (accessed [today's date]).

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