Is CCDC73 p.Ser923Arg (c.2767A>C) pathogenic?

CCDC73 p.Ser923Arg (c.2767A>C) is classified Uncertain significance in CCDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-31). AlphaMissense: likely benign (0.293); Very rare (popmax 0.00167%, amr).

How common is CCDC73 p.Ser923Arg (c.2767A>C) in the general population?

CCDC73 p.Ser923Arg (c.2767A>C) is very rare (popmax 0.00167%, amr) (gnomAD).

What do computational predictors say about CCDC73 p.Ser923Arg (c.2767A>C)?

AlphaMissense predicts likely benign (score 0.293) — an in-silico prediction, not a clinical call.

CCDC73 p.Ser923Arg

c.2767A>C · VCV3486895

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.293 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00167%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.293	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -8.36	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 1.5	GERP 0.44, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 157 kb · p 5.1e-05 · regional, not allelic
Overall
CADD	13.75	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

Grpmax group 0.00167% Admixed American · 1/59,994 alleles

Filtering AF 6.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.9e-05%

Overall 0.000372% 6/1,614,048 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00167%	59,994
African / African-American	0.00133%	74,944
South Asian	0.0011%	91,090
European (non-Finnish)	0.000254%	393,340

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: CCDC73
Protein: p.Ser923Arg
Coding: c.2767A>C
MANE Select: NM_001008391
Type: single nucleotide variant
Location: chr11:32613551 (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.Ser923Ile Likely benign ★ same residue
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

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-ser923arg (accessed [today's date]).

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