Is PASK p.Val1302Ile (c.3904G>A) pathogenic?

PASK p.Val1302Ile (c.3904G>A) is classified Uncertain significance in PASK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.091); Ultra-rare (popmax 0.0903%, nfe).

How common is PASK p.Val1302Ile (c.3904G>A) in the general population?

PASK p.Val1302Ile (c.3904G>A) is ultra-rare (popmax 0.0903%, nfe) (gnomAD).

What do computational predictors say about PASK p.Val1302Ile (c.3904G>A)?

AlphaMissense predicts likely benign (score 0.091) — an in-silico prediction, not a clinical call.

PASK p.Val1302Ile

c.3904G>A · VCV4131293

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.091 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0903%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.091	likely benign
REVEL	0.068	moderately benign-leaning
SaProt	LLR -8.01	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 -2.4	GERP -1.9
Regional constraint	o/e 0.89	unconstrained · MANE · 18 kb · p 0.01 · regional, not allelic
Overall
CADD	1.892	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 0.0903% European (non-Finnish) · 1,066/1,180,026 alleles

Filtering AF 0.0858% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.084%

Overall 0.0709% 1,144/1,614,190 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0903%	1,107
Remaining individualsnot grpmax-eligible	0.0432%	2,315
Admixed American	0.0366%	2,729
African / African-American	0.0266%	3,753
Finnishnot grpmax-eligible	0.0141%	7,113

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: PASK
Protein: p.Val1302Ile
Coding: c.3904G>A
MANE Select: NM_015148
Type: single nucleotide variant
Location: chr2:241106634 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.14 · 2 PDB
Residue 1302: the 'disordered' region

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

Similar variants

PASK c.3533+1G>A Uncertain significance ★★ same type
PASK p.Arg1319His Benign ★★ same type
PASK p.Arg937His Benign ★★ same type
PASK p.Gly782Arg Benign ★★ same type
PASK p.Pro101= Benign ★★ same type
PASK p.Pro844= Benign ★★ same type
PASK p.Ser582= Benign ★★ same type
PASK p.Ser789= Benign ★★ 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/pask-p-val1302ile (accessed [today's date]).

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