Is NOM1 p.Pro104Arg (c.311C>G) pathogenic?

NOM1 p.Pro104Arg (c.311C>G) is classified Uncertain significance in NOM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-08). AlphaMissense: likely benign (0.0686); Ultra-rare (popmax 0.0196%, amr).

How common is NOM1 p.Pro104Arg (c.311C>G) in the general population?

NOM1 p.Pro104Arg (c.311C>G) is ultra-rare (popmax 0.0196%, amr) (gnomAD).

What do computational predictors say about NOM1 p.Pro104Arg (c.311C>G)?

AlphaMissense predicts likely benign (score 0.0686) — an in-silico prediction, not a clinical call.

NOM1 p.Pro104Arg

c.311C>G · rs147347140 · VCV3201131

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0686 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0196%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0686	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -6.36	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 0.48	GERP 1.2, phastCons 0.001
Regional constraint	o/e 1.08	unconstrained · MANE · 20 kb · p 0.0051 · regional, not allelic
Overall
CADD	4.925	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 0.0196% Admixed American · 10/51,024 alleles

Filtering AF 0.0106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00809%

Overall 0.00168% 26/1,543,134 alleles · ultra-rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0196%	5,102
Middle Eastern	0.0171%	5,846
Remaining individualsnot grpmax-eligible	0.00333%	30,009
European (non-Finnish)	0.00113%	88,222

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: NOM1
Protein: p.Pro104Arg
Coding: c.311C>G
MANE Select: NM_138400
dbSNP: rs147347140
Type: single nucleotide variant
Location: chr7:156950048 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.73
Residue 104: the 'necessary for nucleolar localization and for targeting ppp1ca to the nucleolus' region; the 'disordered' region

Full NOM1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NOM1 p.Ala102Val Uncertain significance ★ ⚠ same type
NOM1 p.Ala133Val Uncertain significance ★ ⚠ same type
NOM1 p.Ala156Val Uncertain significance ★ ⚠ same type
NOM1 p.Ala164Thr Uncertain significance ★ ⚠ same type
NOM1 p.Ala166Val Uncertain significance ★ ⚠ same type
NOM1 p.Ala168Thr Uncertain significance ★ ⚠ same type
NOM1 p.Ala170Thr Uncertain significance ★ ⚠ same type
NOM1 p.Ala273Gly 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/nom1-p-pro104arg (accessed [today's date]).

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