Is CC2D1B p.Thr142Ile (c.425C>T) pathogenic?

CC2D1B p.Thr142Ile (c.425C>T) is classified Likely benign in CC2D1B (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-24). AlphaMissense: likely benign (0.0736); Absent from gnomAD v4.1.

How common is CC2D1B p.Thr142Ile (c.425C>T) in the general population?

CC2D1B p.Thr142Ile (c.425C>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CC2D1B p.Thr142Ile (c.425C>T)?

AlphaMissense predicts likely benign (score 0.0736) — an in-silico prediction, not a clinical call.

CC2D1B p.Thr142Ile

c.425C>T · rs1253498251 · VCV3138158

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0736 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0736	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -8.03	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 -0.99	GERP -3.2
Regional constraint	o/e 1.04	unconstrained · MANE · 11 kb · p 0.15 · regional, not allelic
Overall
CADD	0.219	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

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: CC2D1B
Protein: p.Thr142Ile
Coding: c.425C>T
MANE Select: NM_001330585
dbSNP: rs1253498251
Type: single nucleotide variant
Location: chr1:52361026 (GRCh38)
Gene constraint: LOEUF 0.978 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.98
Residue 142: the 'disordered' region

Full CC2D1B gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CC2D1B p.Thr142Ser Uncertain significance ★ ⚠ same residue
CC2D1B p.Gly790= Benign ★★ same type
CC2D1B p.His674Tyr Likely benign ★★ same type
CC2D1B p.Leu511= Benign ★★ same type
CC2D1B p.Ala103Gly Uncertain significance ★ ⚠ same type
CC2D1B p.Ala180Ser Uncertain significance ★ ⚠ same type
CC2D1B p.Ala181Thr Uncertain significance ★ ⚠ same type
CC2D1B p.Ala181Val 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/cc2d1b-p-thr142ile (accessed [today's date]).

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