Is NOM1 p.Pro340Gln (c.1019C>A) pathogenic?

NOM1 p.Pro340Gln (c.1019C>A) is classified Uncertain significance in NOM1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-29). AlphaMissense: ambiguous (0.4041); Absent from gnomAD v4.1.

How common is NOM1 p.Pro340Gln (c.1019C>A) in the general population?

NOM1 p.Pro340Gln (c.1019C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NOM1 p.Pro340Gln (c.1019C>A)?

AlphaMissense predicts ambiguous (score 0.4041) — an in-silico prediction, not a clinical call.

NOM1 p.Pro340Gln

c.1019C>A · VCV3920818

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4041 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Computational evidence

Protein change
AlphaMissense	0.4041	ambiguous
REVEL	0.365	indeterminate
SaProt	LLR -14.30	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.1	GERP 1, phastCons 0.94
Regional constraint	o/e 1.08	unconstrained · MANE · 20 kb · p 0.0051 · regional, not allelic
Overall
CADD	23.4	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: NOM1
Protein: p.Pro340Gln
Coding: c.1019C>A
MANE Select: NM_138400
Type: single nucleotide variant
Location: chr7:156952505 (GRCh38)
Gene constraint: LOEUF 0.961 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.73

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-pro340gln (accessed [today's date]).

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