Is CNPPD1 p.Thr331Ala (c.991A>G) pathogenic?

CNPPD1 p.Thr331Ala (c.991A>G) is classified Uncertain significance in CNPPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-16). AlphaMissense: likely benign (0.0605); Absent from gnomAD v4.1.

How common is CNPPD1 p.Thr331Ala (c.991A>G) in the general population?

CNPPD1 p.Thr331Ala (c.991A>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CNPPD1 p.Thr331Ala (c.991A>G)?

AlphaMissense predicts likely benign (score 0.0605) — an in-silico prediction, not a clinical call.

CNPPD1 p.Thr331Ala

c.991A>G · rs1192915544 · VCV2311947

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0605 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0605	likely benign
REVEL	0.051	moderately benign-leaning
SaProt	LLR -5.86	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 -0.9	GERP -3
Regional constraint	o/e 0.99	unconstrained · MANE · 4,239 bp · p 0.74 · regional, not allelic
Overall
CADD	7.412	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CNPPD1
Protein: p.Thr331Ala
Coding: c.991A>G
MANE Select: NM_015680
dbSNP: rs1192915544
Type: single nucleotide variant
Location: chr2:219172828 (GRCh38)
Gene constraint: LOEUF 1.039 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.88

Full CNPPD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CNPPD1 p.Ala150Val Uncertain significance ★ ⚠ same type
CNPPD1 p.Ala155Thr Uncertain significance ★ ⚠ same type
CNPPD1 p.Ala161Val Uncertain significance ★ ⚠ same type
CNPPD1 p.Ala236Val Uncertain significance ★ ⚠ same type
CNPPD1 p.Ala246Val Uncertain significance ★ ⚠ same type
CNPPD1 p.Ala248Thr Uncertain significance ★ ⚠ same type
CNPPD1 p.Ala293Thr Uncertain significance ★ ⚠ same type
CNPPD1 p.Ala351Thr 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/cnppd1-p-thr331ala (accessed [today's date]).

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