Is CNPPD1 p.Arg306Gln (c.917G>A) pathogenic?

CNPPD1 p.Arg306Gln (c.917G>A) is classified Uncertain significance in CNPPD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-14). AlphaMissense: likely benign (0.0684); Ultra-rare (popmax 0.016%, afr).

How common is CNPPD1 p.Arg306Gln (c.917G>A) in the general population?

CNPPD1 p.Arg306Gln (c.917G>A) is ultra-rare (popmax 0.016%, afr) (gnomAD).

What do computational predictors say about CNPPD1 p.Arg306Gln (c.917G>A)?

AlphaMissense predicts likely benign (score 0.0684) — an in-silico prediction, not a clinical call.

CNPPD1 p.Arg306Gln

c.917G>A · VCV4230976

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0684 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.016%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0684	likely benign
REVEL	0.021	moderately benign-leaning
SaProt	LLR -5.94	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 -2.4	GERP -4.5
Regional constraint	o/e 0.99	unconstrained · MANE · 4,239 bp · p 0.74 · regional, not allelic
Overall
CADD	8.36	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

Grpmax group 0.016% African / African-American · 12/74,814 alleles

Filtering AF 0.00923% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00723%

Overall 0.00174% 28/1,609,682 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.016%	6,234
East Asian	0.00669%	14,949
South Asian	0.00332%	30,151
European (non-Finnish)	0.000849%	117,770

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: CNPPD1
Protein: p.Arg306Gln
Coding: c.917G>A
MANE Select: NM_015680
Type: single nucleotide variant
Location: chr2:219172902 (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-arg306gln (accessed [today's date]).

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