Is CCDC112 p.Phe239Leu (c.717C>A) pathogenic?

CCDC112 p.Phe239Leu (c.717C>A) is classified Uncertain significance in CCDC112 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-26). AlphaMissense: likely pathogenic (0.9472); Very rare (popmax 0.000205%).

How common is CCDC112 p.Phe239Leu (c.717C>A) in the general population?

CCDC112 p.Phe239Leu (c.717C>A) is very rare (popmax 0.000205%) (gnomAD).

What do computational predictors say about CCDC112 p.Phe239Leu (c.717C>A)?

AlphaMissense predicts likely pathogenic (score 0.9472) — an in-silico prediction, not a clinical call.

CCDC112 p.Phe239Leu

c.717C>A · VCV4648935

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9472 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000205%)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9472	likely pathogenic · top 1% in CCDC112
REVEL	0.19	benign-leaning
SaProt	LLR -10.57	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.3	GERP 2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 29 kb · p 0.025 · regional, not allelic
Overall
CADD	23.9	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM F156L vs ClinVar F239L) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.000205%

Overall 0.000205% 3/1,461,778 alleles · very rare

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: CCDC112
Protein: p.Phe239Leu
Coding: c.717C>A
MANE Select: NM_001040440
Type: single nucleotide variant
Location: chr5:115275417 (GRCh38)
Gene constraint: LOEUF 0.875 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 82.18

Full CCDC112 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC112 p.Ala165Val Uncertain significance ★ ⚠ same type
CCDC112 p.Ala299Ser Uncertain significance ★ ⚠ same type
CCDC112 p.Ala434Pro Uncertain significance ★ ⚠ same type
CCDC112 p.Ala68Pro Uncertain significance ★ same type
CCDC112 p.Arg391Cys Uncertain significance ★ ⚠ same type
CCDC112 p.Arg391His Uncertain significance ★ ⚠ same type
CCDC112 p.Arg391Leu Uncertain significance ★ ⚠ same type
CCDC112 p.Arg393Leu 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/ccdc112-p-phe239leu (accessed [today's date]).

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