Is CCDC117 p.Phe32Leu (c.94T>C) pathogenic?

CCDC117 p.Phe32Leu (c.94T>C) is classified Uncertain significance in CCDC117 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely pathogenic (0.8128); Ultra-rare (popmax 0.0861%, eas).

How common is CCDC117 p.Phe32Leu (c.94T>C) in the general population?

CCDC117 p.Phe32Leu (c.94T>C) is ultra-rare (popmax 0.0861%, eas) (gnomAD).

What do computational predictors say about CCDC117 p.Phe32Leu (c.94T>C)?

AlphaMissense predicts likely pathogenic (score 0.8128) — an in-silico prediction, not a clinical call.

CCDC117 p.Phe32Leu

c.94T>C · rs1280531513 · VCV2384117

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8128 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0861%, eas)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.8128	likely pathogenic
REVEL	0.087	moderately benign-leaning
SaProt	LLR -4.32	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.5, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 13 kb · p 0.062 · regional, not allelic
Overall
CADD	19.78	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 0.0861% East Asian · 26/30,190 alleles

Filtering AF 0.0603% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0517%

Overall 0.00222% 27/1,218,268 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0861%	1,161
Remaining individualsnot grpmax-eligible	0.00225%	44,452

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.Phe32Leu
Coding: c.94T>C
MANE Select: NM_173510
dbSNP: rs1280531513
Type: single nucleotide variant
Location: chr22:28772943 (GRCh38)
Gene constraint: LOEUF 0.254 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.99
Residue 32: 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-phe32leu (accessed [today's date]).

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