Is NIN p.Pro576= (c.1728G>A) pathogenic?

NIN p.Pro576= (c.1728G>A) is classified Benign/Likely benign in NIN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-02-01). Low-frequency (popmax 4.77%, afr); Associated with Seckel syndrome 7.

What condition is associated with NIN p.Pro576= (c.1728G>A)?

NIN p.Pro576= (c.1728G>A) is associated with Seckel syndrome 7 (ClinVar).

How common is NIN p.Pro576= (c.1728G>A) in the general population?

NIN p.Pro576= (c.1728G>A) is low-frequency (popmax 4.77%, afr) (gnomAD).

NIN p.Pro576=

c.1728G>A · rs61755036 · VCV129780

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

gnomAD v4.1

Rare

low-frequency (popmax 4.77%, afr)

Conditions

Seckel syndrome 7

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.031	moderately benign-leaning
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.48	GERP -1.2, phastCons 0.014
Overall
CADD	8.192	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 4.77% African / African-American · 3,576/75,004 alleles

Filtering AF 4.64% ClinGen BA1/BS1 input FAF95, joint · FAF99 4.58%

Overall 0.249% 4,021/1,613,738 alleles · low-frequency exomes 1,967/1,461,486 · genomes 2,054/152,252 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	4.77%	21
Remaining individualsnot grpmax-eligible	0.285%	351
Admixed American	0.232%	432
Middle Eastern	0.165%	606
East Asian	0.0178%	5,609
South Asian	0.0176%	5,692
European (non-Finnish)	0.00788%	12,685
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,604

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.Pro576=
Coding: c.1728G>A
MANE Select: NM_020921
dbSNP: rs61755036
Type: single nucleotide variant
Location: chr14:50763872 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.47
Residue 576: the 'disordered' region

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-pro576 (accessed [today's date]).

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