Is NIN p.Val1768Phe (c.5302G>T) pathogenic?

NIN p.Val1768Phe (c.5302G>T) is classified Uncertain significance in NIN (ClinVar, Multiple submitters, 4 submitters; last evaluated 2022-05-18). AlphaMissense: likely benign (0.2534); Ultra-rare (popmax 0.0825%, mid); Associated with Seckel syndrome 7.

What condition is associated with NIN p.Val1768Phe (c.5302G>T)?

NIN p.Val1768Phe (c.5302G>T) is associated with Seckel syndrome 7 (ClinVar).

How common is NIN p.Val1768Phe (c.5302G>T) in the general population?

NIN p.Val1768Phe (c.5302G>T) is ultra-rare (popmax 0.0825%, mid) (gnomAD).

What do computational predictors say about NIN p.Val1768Phe (c.5302G>T)?

AlphaMissense predicts likely benign (score 0.2534) — an in-silico prediction, not a clinical call.

NIN p.Val1768Phe

c.5302G>T · rs151233126 · VCV931903

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

AlphaMissense

likely benign

0.2534 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0825%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Seckel syndrome 7

Computational evidence

Protein change
AlphaMissense	0.2534	likely benign
REVEL	0.168	moderately benign-leaning
SaProt	LLR -9.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.28	acceptor gain · deltas
Constraint at this position
Conservation	phyloP 4.8	GERP 1.5, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 48 kb · p 0.87 · regional, not allelic
Overall
CADD	34.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0825% Middle Eastern · 5/6,058 alleles

Filtering AF 0.0324% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.021%

Overall 0.00731% 118/1,613,262 alleles · ultra-rare exomes 109/1,461,018 · genomes 9/152,244 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0825%	1,212
Remaining individualsnot grpmax-eligible	0.016%	6,248
African / African-American	0.016%	6,249
European (non-Finnish)	0.00729%	13,718
Admixed American	0.00668%	14,969
South Asian	0.0011%	91,012

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.Val1768Phe
Coding: c.5302G>T
MANE Select: NM_020921
dbSNP: rs151233126
Type: single nucleotide variant
Location: chr14:50741728 (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 c.1775-26G>C Benign ★★ same condition
NIN c.5628+5T>C Benign ★★ same condition
NIN c.6192+12C>T Benign ★★ same condition
NIN p.Ala872= 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-val1768phe (accessed [today's date]).

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