Is CCDC73 p.Ser929Phe (c.2786C>T) pathogenic?

CCDC73 p.Ser929Phe (c.2786C>T) is classified Likely benign in CCDC73 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-01-01). AlphaMissense: likely benign (0.1535); Rare (popmax 0.775%, mid).

How common is CCDC73 p.Ser929Phe (c.2786C>T) in the general population?

CCDC73 p.Ser929Phe (c.2786C>T) is rare (popmax 0.775%, mid) (gnomAD).

What do computational predictors say about CCDC73 p.Ser929Phe (c.2786C>T)?

AlphaMissense predicts likely benign (score 0.1535) — an in-silico prediction, not a clinical call.

CCDC73 p.Ser929Phe

c.2786C>T · rs149853604 · VCV2641707

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1535 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.775%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1535	likely benign
REVEL	0.095	moderately benign-leaning
SaProt	LLR -9.35	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 7.6	GERP 0.91, phastCons 1
Regional constraint	o/e 0.88	unconstrained · MANE · 157 kb · p 5.1e-05 · regional, not allelic
Overall
CADD	21.7	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

Grpmax group 0.775% Middle Eastern · 47/6,062 alleles

Filtering AF 0.683% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.665%

Overall 0.306% 4,938/1,614,104 alleles · rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.775%	129
South Asian	0.729%	137
European (non-Finnish)	0.322%	310
Remaining individualsnot grpmax-eligible	0.304%	329
Admixed American	0.28%	357
African / African-American	0.068%	1,471
Finnishnot grpmax-eligible	0.0219%	4,573
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,867

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.Ser929Phe
Coding: c.2786C>T
MANE Select: NM_001008391
dbSNP: rs149853604
Type: single nucleotide variant
Location: chr11:32613532 (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-ser929phe (accessed [today's date]).

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