Is PASK p.Arg451Gln (c.1352G>A) pathogenic?

PASK p.Arg451Gln (c.1352G>A) is classified Likely benign in PASK (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-14). AlphaMissense: likely benign (0.0653); Very rare (popmax 0.00667%, afr).

How common is PASK p.Arg451Gln (c.1352G>A) in the general population?

PASK p.Arg451Gln (c.1352G>A) is very rare (popmax 0.00667%, afr) (gnomAD).

What do computational predictors say about PASK p.Arg451Gln (c.1352G>A)?

AlphaMissense predicts likely benign (score 0.0653) — an in-silico prediction, not a clinical call.

PASK p.Arg451Gln

c.1352G>A · rs368743806 · VCV3208897

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0653 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0653	likely benign
REVEL	0.018	moderately benign-leaning
SaProt	LLR -6.15	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>A here scores Δ0.53 · evaluated, not missing
Constraint at this position
Conservation	phyloP -3.6	GERP -1.8
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.68 · regional, not allelic
Overall
CADD	0.008	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 0.00667% African / African-American · 5/75,008 alleles

Filtering AF 0.00255% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00161%

Overall 0.000867% 14/1,614,062 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00667%	15,002
East Asian	0.00446%	22,439
Remaining individualsnot grpmax-eligible	0.0016%	62,504
European (non-Finnish)	0.000508%	196,661

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.Arg451Gln
Coding: c.1352G>A
MANE Select: NM_015148
dbSNP: rs368743806
Type: single nucleotide variant
Location: chr2:241132985 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.14 · 2 PDB

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-arg451gln (accessed [today's date]).

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