Is NRIP1 p.Ser992= (c.2976C>T) pathogenic?

NRIP1 p.Ser992= (c.2976C>T) is classified Benign in NRIP1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-30). Common (popmax 7.06%, afr) — too common for a highly-penetrant pathogenic allele.

NRIP1 p.Ser992=

Q: How common is NRIP1 p.Ser992= (c.2976C>T) in the general population?

NRIP1 p.Ser992= (c.2976C>T) is common (popmax 7.06%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2976C>T · rs28587162 · VCV778900

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Common

common (popmax 7.06%, afr) — too common for a highly-penetrant pathogenic allele

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 1	GERP 0.25
Overall
CADD	1.75	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 7.06% African / African-American · 5,297/75,008 alleles

Filtering AF 6.9% ClinGen BA1/BS1 input FAF95, joint · FAF99 6.84%

Overall 0.387% 6,243/1,613,888 alleles · common exomes 3,172/1,461,640 · genomes 3,071/152,248 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	7.06%	14
Admixed American	0.617%	162
Remaining individualsnot grpmax-eligible	0.552%	181
Middle Eastern	0.478%	209
South Asian	0.0263%	3,795
European (non-Finnish)	0.015%	6,666
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,594

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: NRIP1
Protein: p.Ser992=
Coding: c.2976C>T
MANE Select: NM_003489
dbSNP: rs28587162
Type: single nucleotide variant
Location: chr21:14965217 (GRCh38)
Gene constraint: LOEUF 0.489 · pLI 0.98 (gnomAD)
Structure: AlphaFold pLDDT 46.10 · 17 PDB
Residue 992: the 'interaction with znf366' region

Full NRIP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

NRIP1 p.Ala1096Gly Uncertain significance ★★ ⚠ same type
NRIP1 p.Ala360Ser Uncertain significance ★★ ⚠ same type
NRIP1 p.Ala36Pro Uncertain significance ★★ ⚠ same type
NRIP1 p.Ala792Val Uncertain significance ★★ ⚠ same type
NRIP1 p.Arg1082Gly Uncertain significance ★★ ⚠ same type
NRIP1 p.Arg1122Gly Uncertain significance ★★ ⚠ same type
NRIP1 p.Arg98Trp Uncertain significance ★★ ⚠ same type
NRIP1 p.Asn45Asp 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/nrip1-p-ser992 (accessed [today's date]).

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