Is CCDC112 p.Asp251Val (c.752A>T) pathogenic?

CCDC112 p.Asp251Val (c.752A>T) is classified Uncertain significance in CCDC112 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-05). AlphaMissense: ambiguous (0.3885); Ultra-rare (popmax 0.0136%, nfe).

How common is CCDC112 p.Asp251Val (c.752A>T) in the general population?

CCDC112 p.Asp251Val (c.752A>T) is ultra-rare (popmax 0.0136%, nfe) (gnomAD).

What do computational predictors say about CCDC112 p.Asp251Val (c.752A>T)?

AlphaMissense predicts ambiguous (score 0.3885) — an in-silico prediction, not a clinical call.

CCDC112 p.Asp251Val

c.752A>T · rs148058501 · VCV2341528

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3885 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0136%, nfe)

Computational evidence

Protein change
AlphaMissense	0.3885	ambiguous
REVEL	0.4	indeterminate
SaProt	LLR -14.07	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.1	GERP 2, phastCons 1
Regional constraint	o/e 1.09	unconstrained · MANE · 29 kb · p 0.025 · regional, not allelic
Overall
CADD	26.6	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 D168V vs ClinVar D251V) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0136% European (non-Finnish) · 161/1,179,998 alleles

Filtering AF 0.0119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0112%

Overall 0.0103% 166/1,613,976 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0136%	7,329
Remaining individualsnot grpmax-eligible	0.0048%	20,827
Admixed American	0.00167%	59,992
African / African-American	0.00133%	74,908

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.Asp251Val
Coding: c.752A>T
MANE Select: NM_001040440
dbSNP: rs148058501
Type: single nucleotide variant
Location: chr5:115275382 (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-asp251val (accessed [today's date]).

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