Is NOG p.Arg34Pro (c.101G>C) pathogenic?

NOG p.Arg34Pro (c.101G>C) is classified Uncertain significance in NOG (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-11-04). AlphaMissense: likely pathogenic (0.9854); Absent from gnomAD v4.1; Associated with proximal symphalangism 1A.

What condition is associated with NOG p.Arg34Pro (c.101G>C)?

NOG p.Arg34Pro (c.101G>C) is associated with proximal symphalangism 1A (ClinVar).

How common is NOG p.Arg34Pro (c.101G>C) in the general population?

NOG p.Arg34Pro (c.101G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NOG p.Arg34Pro (c.101G>C)?

AlphaMissense predicts likely pathogenic (score 0.9854) — an in-silico prediction, not a clinical call.

NOG p.Arg34Pro

c.101G>C · rs763181672 · VCV2573208

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9854 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

proximal symphalangism 1A

Computational evidence

Protein change
AlphaMissense	0.9854	likely pathogenic
REVEL	0.644	pathogenic-leaning
SaProt	LLR -7.75	tolerated
⇒ AlphaMissense and REVEL call this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.6	GERP 0.65, phastCons 1
Regional constraint	o/e 0.97	unconstrained · MANE · 436 bp · p 0.69 · regional, not allelic
Overall
CADD	25.4	PHRED · no single calibrated threshold — expert panels disagree

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: NOG
Protein: p.Arg34Pro
Coding: c.101G>C
MANE Select: NM_005450
dbSNP: rs763181672
Type: single nucleotide variant
Location: chr17:56594324 (GRCh38)
Gene constraint: LOEUF 0.367 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 87.40 · 2 PDB

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

Disease context

proximal symphalangism 1A — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NOG p.Arg34Leu Uncertain significance ★ ⚠ same residue
NOG p.Pro35Arg Pathogenic/Likely pathogenic ★★ ⚠ same condition
NOG p.Pro35Ser Pathogenic ★★ ⚠ same condition
NOG p.Tyr222Cys Pathogenic/Likely pathogenic ★★ same condition
NOG p.Ser185Cys Likely pathogenic ★ same condition
NOG p.Arg182Pro Uncertain significance ★ ⚠ same condition
NOG p.Arg204Gln Conflicting classifications of pathogenicity ★ ⚠ same condition
NOG p.Pro223Arg Uncertain significance ★ ⚠ same condition

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/nog-p-arg34pro (accessed [today's date]).

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