Is CCDC73 p.Ser679Pro (c.2035T>C) pathogenic?

CCDC73 p.Ser679Pro (c.2035T>C) is classified Uncertain significance in CCDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-26). AlphaMissense: likely benign (0.0632); Absent from gnomAD v4.1.

How common is CCDC73 p.Ser679Pro (c.2035T>C) in the general population?

CCDC73 p.Ser679Pro (c.2035T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC73 p.Ser679Pro (c.2035T>C)?

AlphaMissense predicts likely benign (score 0.0632) — an in-silico prediction, not a clinical call.

CCDC73 p.Ser679Pro

c.2035T>C · VCV4649657

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0632 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0632	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -6.24	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 1.8	GERP -3.1, phastCons 0.21
Regional constraint	o/e 0.88	unconstrained · MANE · 157 kb · p 5.1e-05 · regional, not allelic
Overall
CADD	5.738	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

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: CCDC73
Protein: p.Ser679Pro
Coding: c.2035T>C
MANE Select: NM_001008391
Type: single nucleotide variant
Location: chr11:32614283 (GRCh38)
Gene constraint: LOEUF 1.103 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.16

Full CCDC73 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC73 p.Ala220Glu Uncertain significance ★ ⚠ same type
CCDC73 p.Ala221Val Uncertain significance ★ ⚠ same type
CCDC73 p.Ala614Val Uncertain significance ★ ⚠ same type
CCDC73 p.Ala717Val Uncertain significance ★ ⚠ same type
CCDC73 p.Ala789Thr Uncertain significance ★ ⚠ same type
CCDC73 p.Ala88Thr Uncertain significance ★ ⚠ same type
CCDC73 p.Ala974Asp Uncertain significance ★ ⚠ same type
CCDC73 p.Arg292Trp 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/ccdc73-p-ser679pro (accessed [today's date]).

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