Is CCDC117 p.Pro45Ser (c.133C>T) pathogenic?

CCDC117 p.Pro45Ser (c.133C>T) is classified Likely benign in CCDC117 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-12-16). AlphaMissense: likely benign (0.0872); Very rare (popmax 0.000103%, nfe).

How common is CCDC117 p.Pro45Ser (c.133C>T) in the general population?

CCDC117 p.Pro45Ser (c.133C>T) is very rare (popmax 0.000103%, nfe) (gnomAD).

What do computational predictors say about CCDC117 p.Pro45Ser (c.133C>T)?

AlphaMissense predicts likely benign (score 0.0872) — an in-silico prediction, not a clinical call.

CCDC117 p.Pro45Ser

c.133C>T · VCV4829861

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0872 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000103%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0872	likely benign
REVEL	0.031	moderately benign-leaning
SaProt	LLR -6.88	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 0.17	GERP -1.7, phastCons 0.082
Regional constraint	o/e 1.10	unconstrained · MANE · 13 kb · p 0.062 · regional, not allelic
Overall
CADD	12.09	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 0.000103% European (non-Finnish) · 1/968,400 alleles

Overall 0.000286% 3/1,050,470 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00614%	16,280
Remaining individualsnot grpmax-eligible	0.0023%	43,438
European (non-Finnish)grpmax	0.000103%	968,401

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: CCDC117
Protein: p.Pro45Ser
Coding: c.133C>T
MANE Select: NM_173510
Type: single nucleotide variant
Location: chr22:28772982 (GRCh38)
Gene constraint: LOEUF 0.254 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.99
Residue 45: the 'disordered' region

Full CCDC117 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC117 p.Ala55Val Uncertain significance ★ ⚠ same type
CCDC117 p.Arg146Gln Uncertain significance ★ ⚠ same type
CCDC117 p.Arg203Cys Uncertain significance ★ ⚠ same type
CCDC117 p.Arg203His Uncertain significance ★ ⚠ same type
CCDC117 p.Arg44Trp Uncertain significance ★ ⚠ same type
CCDC117 p.Arg48His Uncertain significance ★ ⚠ same type
CCDC117 p.Arg62Cys Uncertain significance ★ ⚠ same type
CCDC117 p.Arg6Gly 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/ccdc117-p-pro45ser (accessed [today's date]).

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