Is CCDC112 p.Leu511Val (c.1531C>G) pathogenic?

CCDC112 p.Leu511Val (c.1531C>G) is classified Uncertain significance in CCDC112 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: likely benign (0.1106); Ultra-rare (popmax 0.0287%, nfe).

How common is CCDC112 p.Leu511Val (c.1531C>G) in the general population?

CCDC112 p.Leu511Val (c.1531C>G) is ultra-rare (popmax 0.0287%, nfe) (gnomAD).

What do computational predictors say about CCDC112 p.Leu511Val (c.1531C>G)?

AlphaMissense predicts likely benign (score 0.1106) — an in-silico prediction, not a clinical call.

CCDC112 p.Leu511Val

c.1531C>G · VCV3485893

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1106 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0287%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1106	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -5.93	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 2.6	GERP 0.19, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 29 kb · p 0.025 · regional, not allelic
Overall
CADD	19.85	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM L428V vs ClinVar L511V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0287% European (non-Finnish) · 336/1,169,704 alleles

Filtering AF 0.0262% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0252%

Overall 0.0232% 370/1,593,890 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0287%	3,481
South Asian	0.0203%	4,930
Remaining individualsnot grpmax-eligible	0.0179%	5,594
Middle Eastern	0.0166%	6,032
Admixed American	0.0035%	28,571
African / African-American	0.00271%	36,899

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.Leu511Val
Coding: c.1531C>G
MANE Select: NM_001040440
Type: single nucleotide variant
Location: chr5:115268898 (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-leu511val (accessed [today's date]).

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