Is CCDC112 p.Val334Met (c.1000G>A) pathogenic?

CCDC112 p.Val334Met (c.1000G>A) is classified Likely benign in CCDC112 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-06-21). AlphaMissense: likely benign (0.0616); Very rare (popmax 0.00246%, nfe).

How common is CCDC112 p.Val334Met (c.1000G>A) in the general population?

CCDC112 p.Val334Met (c.1000G>A) is very rare (popmax 0.00246%, nfe) (gnomAD).

What do computational predictors say about CCDC112 p.Val334Met (c.1000G>A)?

AlphaMissense predicts likely benign (score 0.0616) — an in-silico prediction, not a clinical call.

CCDC112 p.Val334Met

c.1000G>A · rs765762178 · VCV2234036

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0616 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00246%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0616	likely benign
REVEL	0.017	moderately benign-leaning
SaProt	LLR -8.02	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 -5.1	GERP -3.6
Regional constraint	o/e 1.09	unconstrained · MANE · 29 kb · p 0.025 · regional, not allelic
Overall
CADD	0.005	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 V251M vs ClinVar V334M) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00246% European (non-Finnish) · 29/1,178,708 alleles

Filtering AF 0.00173% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00149%

Overall 0.00199% 32/1,608,376 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00246%	40,645
East Asian	0.00224%	44,730
Admixed American	0.0017%	58,792
Remaining individualsnot grpmax-eligible	0.00161%	62,282

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.Val334Met
Coding: c.1000G>A
MANE Select: NM_001040440
dbSNP: rs765762178
Type: single nucleotide variant
Location: chr5:115271545 (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-val334met (accessed [today's date]).

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