Is CCDC175 p.Arg693Pro (c.2078G>C) pathogenic?

CCDC175 p.Arg693Pro (c.2078G>C) is classified Uncertain significance in CCDC175 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-09-12). AlphaMissense: ambiguous (0.4136); Absent from gnomAD v4.1.

How common is CCDC175 p.Arg693Pro (c.2078G>C) in the general population?

CCDC175 p.Arg693Pro (c.2078G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC175 p.Arg693Pro (c.2078G>C)?

AlphaMissense predicts ambiguous (score 0.4136) — an in-silico prediction, not a clinical call.

CCDC175 p.Arg693Pro

c.2078G>C · rs73305628 · VCV2622715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4136 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4136	ambiguous
REVEL	0.052	moderately benign-leaning
SaProt	LLR -11.35	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.8	GERP -2.6, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 72 kb · p 0.21 · regional, not allelic
Overall
CADD	15.23	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: CCDC175
Protein: p.Arg693Pro
Coding: c.2078G>C
MANE Select: NM_001164399
dbSNP: rs73305628
Type: single nucleotide variant
Location: chr14:59521594 (GRCh38)
Gene constraint: LOEUF 1.235 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 76.01

Full CCDC175 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC175 p.Ala124Thr Uncertain significance ★ ⚠ same type
CCDC175 p.Ala219Val Uncertain significance ★ ⚠ same type
CCDC175 p.Ala228Pro Uncertain significance ★ ⚠ same type
CCDC175 p.Ala316Val Uncertain significance ★ ⚠ same type
CCDC175 p.Ala353Pro Uncertain significance ★ ⚠ same type
CCDC175 p.Ala429Ser Uncertain significance ★ ⚠ same type
CCDC175 p.Arg122Gln Uncertain significance ★ ⚠ same type
CCDC175 p.Arg206Gly 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/ccdc175-p-arg693pro (accessed [today's date]).

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