Is CCDC178 p.Thr373Pro (c.1117A>C) pathogenic?

CCDC178 p.Thr373Pro (c.1117A>C) is classified Uncertain significance in CCDC178 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-12). AlphaMissense: ambiguous (0.4305); Absent from gnomAD v4.1.

How common is CCDC178 p.Thr373Pro (c.1117A>C) in the general population?

CCDC178 p.Thr373Pro (c.1117A>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC178 p.Thr373Pro (c.1117A>C)?

AlphaMissense predicts ambiguous (score 0.4305) — an in-silico prediction, not a clinical call.

CCDC178 p.Thr373Pro

c.1117A>C · rs759622933 · VCV2254134

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4305 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4305	ambiguous
REVEL	0.129	moderately benign-leaning
SaProt	LLR -9.00	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.18	GERP 0.78
Regional constraint	o/e 1.04	unconstrained · MANE · 474 kb · p 0.17 · regional, not allelic
Overall
CADD	12.49	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: CCDC178
Protein: p.Thr373Pro
Coding: c.1117A>C
MANE Select: NM_001105528
dbSNP: rs759622933
Type: single nucleotide variant
Location: chr18:33293218 (GRCh38)
Gene constraint: LOEUF 1.347 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.69

Full CCDC178 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC178 p.Lys515Arg Uncertain significance ★★ ⚠ same type
CCDC178 p.Ala216Thr Uncertain significance ★ ⚠ same type
CCDC178 p.Ala261Gly Uncertain significance ★ ⚠ same type
CCDC178 p.Ala339Asp Uncertain significance ★ ⚠ same type
CCDC178 p.Ala339Thr Uncertain significance ★ ⚠ same type
CCDC178 p.Ala375Thr Uncertain significance ★ ⚠ same type
CCDC178 p.Ala563Thr Uncertain significance ★ ⚠ same type
CCDC178 p.Ala574Glu 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/ccdc178-p-thr373pro (accessed [today's date]).

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