Is NIN p.Ala1049Pro (c.3145G>C) pathogenic?

NIN p.Ala1049Pro (c.3145G>C) is classified Uncertain significance in NIN (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-04). AlphaMissense: likely benign (0.1338); Absent from gnomAD v4.1.

How common is NIN p.Ala1049Pro (c.3145G>C) in the general population?

NIN p.Ala1049Pro (c.3145G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NIN p.Ala1049Pro (c.3145G>C)?

AlphaMissense predicts likely benign (score 0.1338) — an in-silico prediction, not a clinical call.

NIN p.Ala1049Pro

c.3145G>C · VCV3696022

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1338 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1338	likely benign
REVEL	0.101	moderately benign-leaning
SaProt	LLR -6.72	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 -0.26	GERP -1.2
Regional constraint	o/e 1.00	unconstrained · MANE · 48 kb · p 0.87 · regional, not allelic
Overall
CADD	14.1	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.Ala1049Pro
Coding: c.3145G>C
MANE Select: NM_020921
Type: single nucleotide variant
Location: chr14:50757885 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.47
Residue 1049: the 'important for interaction with cep170' region; the 'interacts with dsp' region

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

Similar variants

NIN p.Ala1049Thr Uncertain significance ★★ ⚠ same residue
NIN p.Arg2039Ter Likely pathogenic ★★ 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
NIN p.Ala1813Gly 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-ala1049pro (accessed [today's date]).

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