Is NIN p.Ser1972= (c.5916C>T) pathogenic?

NIN p.Ser1972= (c.5916C>T) is classified Likely benign in NIN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-09-30). Very rare (popmax 0.0044%, sas).

How common is NIN p.Ser1972= (c.5916C>T) in the general population?

NIN p.Ser1972= (c.5916C>T) is very rare (popmax 0.0044%, sas) (gnomAD).

NIN p.Ser1972=

c.5916C>T · VCV4709094

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.0044%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.037	moderately benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 3.3	GERP 0.62, phastCons 1
Overall
CADD	4.947	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0044% South Asian · 4/90,826 alleles

Filtering AF 0.00143% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000893%

Overall 0.000248% 4/1,612,788 alleles · very rare exomes 4/1,460,456 · genomes 0/152,332 · 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.Ser1972=
Coding: c.5916C>T
MANE Select: NM_020921
Type: single nucleotide variant
Location: chr14:50729685 (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.Ser1972Phe Uncertain significance ★ ⚠ 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-ser1972 (accessed [today's date]).

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