Is NIN p.Ala996Val (c.2987C>T) pathogenic?

NIN p.Ala996Val (c.2987C>T) is classified Likely benign in NIN (ClinVar, Multiple submitters, 5 submitters; last evaluated 2026-01-15). AlphaMissense: likely benign (0.072); Rare (popmax 0.475%, nfe).

How common is NIN p.Ala996Val (c.2987C>T) in the general population?

NIN p.Ala996Val (c.2987C>T) is rare (popmax 0.475%, nfe) (gnomAD).

What do computational predictors say about NIN p.Ala996Val (c.2987C>T)?

AlphaMissense predicts likely benign (score 0.072) — an in-silico prediction, not a clinical call.

NIN p.Ala996Val

c.2987C>T · rs41313507 · VCV211604

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 5 submitters

AlphaMissense

likely benign

0.072 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.475%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.072	likely benign
REVEL	0.045	moderately benign-leaning
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.3	GERP -2.8
Regional constraint	o/e 1.00	unconstrained · MANE · 48 kb · p 0.87 · regional, not allelic
Overall
CADD	0.07	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

Grpmax group 0.475% European (non-Finnish) · 5,602/1,180,026 alleles

Filtering AF 0.464% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.46%

Overall 0.381% 6,156/1,614,162 alleles · rare exomes 5,795/1,461,886 · genomes 361/152,276 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.475%	211
Remaining individualsnot grpmax-eligible	0.419%	239
Admixed American	0.205%	488
Middle Eastern	0.099%	1,010
Finnishnot grpmax-eligible	0.0719%	1,392
African / African-American	0.0693%	1,443
South Asian	0.0604%	1,656
Ashkenazi Jewishnot grpmax-eligible	0.0304%	3,290
East Asian	0.00223%	44,876

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.Ala996Val
Coding: c.2987C>T
MANE Select: NM_020921
dbSNP: rs41313507
Type: single nucleotide variant
Location: chr14:50758043 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.47
Residue 996: the 'important for interaction with cep170' region

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

Similar variants

NIN p.Ala996= Benign ★★ same residue
NIN p.Ala996Gly 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

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-ala996val (accessed [today's date]).

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