Is NIN p.Ser1338= (c.4014C>T) pathogenic?

NIN p.Ser1338= (c.4014C>T) is classified Likely benign in NIN (ClinVar, No assertion criteria, 1 submitter; last evaluated 2019-04-12). Rare (popmax 0.274%, sas); Associated with NIN-related disorder.

What condition is associated with NIN p.Ser1338= (c.4014C>T)?

NIN p.Ser1338= (c.4014C>T) is associated with NIN-related disorder (ClinVar).

How common is NIN p.Ser1338= (c.4014C>T) in the general population?

NIN p.Ser1338= (c.4014C>T) is rare (popmax 0.274%, sas) (gnomAD).

NIN p.Ser1338=

c.4014C>T · rs533886131 · VCV3043291

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

rare (popmax 0.274%, sas)

Conditions

NIN-related disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.012	strongly benign-leaning
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -1.7	GERP -3.7
Overall
CADD	1.202	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.274% South Asian · 249/90,866 alleles

Filtering AF 0.246% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.235%

Overall 0.0168% 271/1,613,032 alleles · rare exomes 257/1,460,776 · genomes 14/152,256 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.274%	365
Middle Eastern	0.0165%	6,052
Remaining individualsnot grpmax-eligible	0.0128%	7,806
African / African-American	0.00267%	37,467
Admixed American	0.00167%	59,754
European (non-Finnish)	0.000848%	117,967

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.Ser1338=
Coding: c.4014C>T
MANE Select: NM_020921
dbSNP: rs533886131
Type: single nucleotide variant
Location: chr14:50757016 (GRCh38)
Gene constraint: LOEUF 0.62 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 64.47
Residue 1338: the 'important for interaction with cep170' region; the 'interacts with dsp' region

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

Disease context

NIN-related disorder

Similar variants

NIN p.Ser1756Cys Uncertain significance ★ ⚠ same condition
NIN p.Asn1831= Likely benign same condition
NIN p.Ser91Leu Likely benign same condition
NIN p.Tyr1311= Likely benign same condition
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

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-ser1338 (accessed [today's date]).

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