Is NIT2 p.Val260Ala (c.779T>C) pathogenic?

NIT2 p.Val260Ala (c.779T>C) is classified Uncertain significance in NIT2 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-04). AlphaMissense: ambiguous (0.3738); Absent from gnomAD v4.1.

How common is NIT2 p.Val260Ala (c.779T>C) in the general population?

NIT2 p.Val260Ala (c.779T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about NIT2 p.Val260Ala (c.779T>C)?

AlphaMissense predicts ambiguous (score 0.3738) — an in-silico prediction, not a clinical call.

NIT2 p.Val260Ala

c.779T>C · rs2472035616 · VCV3200246

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3738 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.3738	ambiguous
REVEL	0.217	benign-leaning
SaProt	LLR -10.49	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.8, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 20 kb · p 0.07 · regional, not allelic
Overall
CADD	24.1	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: NIT2
Protein: p.Val260Ala
Coding: c.779T>C
MANE Select: NM_020202
dbSNP: rs2472035616
Type: single nucleotide variant
Location: chr3:100355216 (GRCh38)
Gene constraint: LOEUF 1.249 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 97.62

Full NIT2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NIT2 p.Ala209Val Uncertain significance ★ ⚠ same type
NIT2 p.Ala51Gly Uncertain significance ★ ⚠ same type
NIT2 p.Ala51Val Uncertain significance ★ ⚠ same type
NIT2 p.Arg157Gln Uncertain significance ★ ⚠ same type
NIT2 p.Arg195Trp Uncertain significance ★ ⚠ same type
NIT2 p.Arg210Trp Uncertain significance ★ same type
NIT2 p.Arg23Cys Uncertain significance ★ ⚠ same type
NIT2 p.Arg255Cys 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/nit2-p-val260ala (accessed [today's date]).

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