Is CCDC117 p.Asp79Glu (c.237T>G) pathogenic?

CCDC117 p.Asp79Glu (c.237T>G) is classified Uncertain significance in CCDC117 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-03-17). AlphaMissense: likely benign (0.0831); Ultra-rare (popmax 0.0267%, eas).

How common is CCDC117 p.Asp79Glu (c.237T>G) in the general population?

CCDC117 p.Asp79Glu (c.237T>G) is ultra-rare (popmax 0.0267%, eas) (gnomAD).

What do computational predictors say about CCDC117 p.Asp79Glu (c.237T>G)?

AlphaMissense predicts likely benign (score 0.0831) — an in-silico prediction, not a clinical call.

CCDC117 p.Asp79Glu

c.237T>G · VCV3996346

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0831 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0267%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0831	likely benign
REVEL	0.112	moderately benign-leaning
SaProt	LLR -4.84	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 -2.9
Regional constraint	o/e 1.10	unconstrained · MANE · 13 kb · p 0.062 · regional, not allelic
Overall
CADD	4.118	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 0.0267% East Asian · 12/44,892 alleles

Filtering AF 0.0154% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0121%

Overall 0.000868% 14/1,612,918 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0267%	3,741
Remaining individualsnot grpmax-eligible	0.0032%	31,230

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.Asp79Glu
Coding: c.237T>G
MANE Select: NM_173510
Type: single nucleotide variant
Location: chr22:28773776 (GRCh38)
Gene constraint: LOEUF 0.254 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 60.99
Residue 79: 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-asp79glu (accessed [today's date]).

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