Is NIN p.Ala582Ser (c.1744G>T) pathogenic?

NIN p.Ala582Ser (c.1744G>T) is classified Uncertain significance in NIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-25). AlphaMissense: likely benign (0.0898); Absent from gnomAD v4.1.

How common is NIN p.Ala582Ser (c.1744G>T) in the general population?

NIN p.Ala582Ser (c.1744G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NIN p.Ala582Ser (c.1744G>T)?

AlphaMissense predicts likely benign (score 0.0898) — an in-silico prediction, not a clinical call.

NIN p.Ala582Ser

c.1744G>T · VCV3405655

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0898 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0898	likely benign
REVEL	0.067	moderately benign-leaning
SaProt	LLR -5.76	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -0.013	GERP -0.84
Regional constraint	o/e 1.00	unconstrained · MANE · 48 kb · p 0.87 · regional, not allelic
Overall
CADD	0.702	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: NIN
Protein: p.Ala582Ser
Coding: c.1744G>T
MANE Select: NM_020921
Type: single nucleotide variant
Location: chr14:50763856 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.47
Residue 582: the 'disordered' region

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

Similar variants

NIN p.Ala582Val Likely benign ★ same residue
NIN p.Arg2039Ter Likely pathogenic ★★ same type
NIN p.Ala1049Thr Uncertain significance ★★ ⚠ same type
NIN p.Ala1212Val Uncertain significance ★★ ⚠ same type
NIN p.Ala1350Gly Uncertain significance ★★ ⚠ same type
NIN p.Ala1741Val Uncertain significance ★★ ⚠ same type
NIN p.Ala1755Thr Uncertain significance ★★ ⚠ same type
NIN p.Ala1755Val 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/nin-p-ala582ser (accessed [today's date]).

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