Is CCDC117 p.Pro51Ser (c.151C>T) pathogenic?

CCDC117 p.Pro51Ser (c.151C>T) is classified Uncertain significance in CCDC117 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-09). AlphaMissense: likely benign (0.0904); Very rare (popmax 0.00898%, amr).

How common is CCDC117 p.Pro51Ser (c.151C>T) in the general population?

CCDC117 p.Pro51Ser (c.151C>T) is very rare (popmax 0.00898%, amr) (gnomAD).

What do computational predictors say about CCDC117 p.Pro51Ser (c.151C>T)?

AlphaMissense predicts likely benign (score 0.0904) — an in-silico prediction, not a clinical call.

CCDC117 p.Pro51Ser

c.151C>T · rs894775503 · VCV3138278

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0904 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00898%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0904	likely benign
REVEL	0.06	moderately benign-leaning
SaProt	LLR -6.46	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 0.74	GERP -0.57
Regional constraint	o/e 1.10	unconstrained · MANE · 13 kb · p 0.062 · regional, not allelic
Overall
CADD	12.12	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 0.00898% Admixed American · 2/22,264 alleles

Filtering AF 0.00159% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000655%

Overall 0.000335% 4/1,193,522 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00898%	11,132
East Asian	0.00354%	28,248
European (non-Finnish)	0.000104%	963,243

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.Pro51Ser
Coding: c.151C>T
MANE Select: NM_173510
dbSNP: rs894775503
Type: single nucleotide variant
Location: chr22:28773000 (GRCh38)
Gene constraint: LOEUF 0.254 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.99
Residue 51: 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-pro51ser (accessed [today's date]).

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