Is NIN p.Trp147Arg (c.439T>C) pathogenic?

NIN p.Trp147Arg (c.439T>C) is classified Uncertain significance in NIN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely pathogenic (0.5771); Very rare (popmax 8.47e-05%, nfe).

How common is NIN p.Trp147Arg (c.439T>C) in the general population?

NIN p.Trp147Arg (c.439T>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about NIN p.Trp147Arg (c.439T>C)?

AlphaMissense predicts likely pathogenic (score 0.5771) — an in-silico prediction, not a clinical call.

NIN p.Trp147Arg

c.439T>C · rs2506194400 · VCV2072771

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5771 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.5771	likely pathogenic
REVEL	0.185	benign-leaning
SaProt	LLR -5.09	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.9	GERP 1.5, phastCons 1
Regional constraint	o/e 0.91	unconstrained · MANE · 51 kb · p 0.051 · regional, not allelic
Overall
CADD	26.2	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

Grpmax group 8.47e-05% European (non-Finnish) · 1/1,179,976 alleles

Overall 6.2e-05% 1/1,614,072 alleles · very rare exomes 1/1,461,806 · genomes 0/152,266 · joint denominator

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: NIN
Protein: p.Trp147Arg
Coding: c.439T>C
MANE Select: NM_020921
dbSNP: rs2506194400
Type: single nucleotide variant
Location: chr14:50778801 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.47

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

Similar variants

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
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-trp147arg (accessed [today's date]).

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