Is NIN p.Val376= (c.1128T>C) pathogenic?

NIN p.Val376= (c.1128T>C) is classified Benign in NIN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-04). Common (popmax 82.7%, eas) — too common for a highly-penetrant pathogenic allele; Associated with Seckel syndrome 7.

What condition is associated with NIN p.Val376= (c.1128T>C)?

NIN p.Val376= (c.1128T>C) is associated with Seckel syndrome 7 (ClinVar).

NIN p.Val376=

Q: How common is NIN p.Val376= (c.1128T>C) in the general population?

NIN p.Val376= (c.1128T>C) is common (popmax 82.7%, eas) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.1128T>C · rs17793018 · VCV129779

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Common

common (popmax 82.7%, eas) — too common for a highly-penetrant pathogenic allele

Conditions

Seckel syndrome 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.17	GERP -3, phastCons 0.003
Overall
CADD	6.392	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 82.7% East Asian · 37,131/44,874 alleles

Filtering AF 82% ClinGen BA1/BS1 input FAF95, joint · FAF99 81.7%

Overall 61.5% 992,220/1,613,166 alleles · common exomes 910,176/1,461,046 · genomes 82,044/152,120 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	82.7%	1
Finnishnot grpmax-eligible	67.5%	1
South Asian	67.4%	1
Admixed American	65.4%	2
Amishnot grpmax-eligible	63.9%	2
European (non-Finnish)	62.1%	2
Remaining individualsnot grpmax-eligible	61%	2
Middle Eastern	54.1%	2
Ashkenazi Jewishnot grpmax-eligible	52.5%	2
African / African-American	28.6%	3

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.Val376=
Coding: c.1128T>C
MANE Select: NM_020921
dbSNP: rs17793018
Type: single nucleotide variant
Location: chr14:50770983 (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

Disease context

Seckel syndrome 7 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

NIN p.Arg2039Ter Likely pathogenic ★★ same condition
NIN p.Ser1009Asn Uncertain significance ★★ ⚠ same condition
NIN p.Thr2092Ile Uncertain significance ★★ same condition
NIN p.Val117Met Uncertain significance ★★ ⚠ same condition
NIN p.Val1768Phe Uncertain significance ★★ ⚠ same condition
NIN c.1775-26G>C Benign ★★ same condition
NIN c.5628+5T>C Benign ★★ same condition
NIN c.6192+12C>T Benign ★★ same condition

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-val376 (accessed [today's date]).

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