Is NIN p.Ala360Val (c.1079C>T) pathogenic?

NIN p.Ala360Val (c.1079C>T) is classified Uncertain significance in NIN (ClinVar, Single submitter, 2 submitters; last evaluated 2025-10-08). AlphaMissense: likely benign (0.3237); Ultra-rare (popmax 0.033%, mid).

How common is NIN p.Ala360Val (c.1079C>T) in the general population?

NIN p.Ala360Val (c.1079C>T) is ultra-rare (popmax 0.033%, mid) (gnomAD).

What do computational predictors say about NIN p.Ala360Val (c.1079C>T)?

AlphaMissense predicts likely benign (score 0.3237) — an in-silico prediction, not a clinical call.

NIN p.Ala360Val

c.1079C>T · rs769471241 · VCV2197492

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3237 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.033%, mid)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.3237	likely benign
REVEL	0.59	indeterminate
SaProt	LLR -3.62	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 1.7, phastCons 1
Regional constraint	o/e 0.38	unconstrained · MANE · 57 bp · p 0.0025 · regional, not allelic
Overall
CADD	32.0	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 0.033% Middle Eastern · 2/6,060 alleles

Filtering AF 0.00582% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00345%

Overall 0.00409% 66/1,614,174 alleles · ultra-rare exomes 56/1,461,854 · genomes 10/152,320 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.033%	3,030
Remaining individualsnot grpmax-eligible	0.008%	12,502
European (non-Finnish)	0.00483%	20,702
Admixed American	0.00167%	60,020
African / African-American	0.00133%	75,046

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.Ala360Val
Coding: c.1079C>T
MANE Select: NM_020921
dbSNP: rs769471241
Type: single nucleotide variant
Location: chr14:50771371 (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

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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-ala360val (accessed [today's date]).

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