Is PASK p.Arg937His (c.2810G>A) pathogenic?

PASK p.Arg937His (c.2810G>A) is classified Benign in PASK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.0913); Rare (popmax 0.816%, nfe).

How common is PASK p.Arg937His (c.2810G>A) in the general population?

PASK p.Arg937His (c.2810G>A) is rare (popmax 0.816%, nfe) (gnomAD).

What do computational predictors say about PASK p.Arg937His (c.2810G>A)?

AlphaMissense predicts likely benign (score 0.0913) — an in-silico prediction, not a clinical call.

PASK p.Arg937His

c.2810G>A · rs56139954 · VCV790259

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0913 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.816%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0913	likely benign
REVEL	0.065	moderately benign-leaning
SaProt	LLR -7.54	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 -2.2	GERP -2.7
Regional constraint	o/e 0.89	unconstrained · MANE · 18 kb · p 0.01 · regional, not allelic
Overall
CADD	12.67	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 0.816% European (non-Finnish) · 9,631/1,179,934 alleles

Filtering AF 0.803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.797%

Overall 0.801% 12,917/1,613,546 alleles · rare

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	4.01%	25
European (non-Finnish)grpmax	0.816%	123
Remaining individualsnot grpmax-eligible	0.57%	175
South Asian	0.237%	422
African / African-American	0.115%	872
Middle Eastern	0.1%	999
Admixed American	0.0883%	1,132
Ashkenazi Jewishnot grpmax-eligible	0.054%	1,850

Finnish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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.Arg937His
Coding: c.2810G>A
MANE Select: NM_015148
dbSNP: rs56139954
Type: single nucleotide variant
Location: chr2:241124043 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.14 · 2 PDB
Residue 937: a UniProt-annotated variant site (in)

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

Similar variants

PASK p.Arg937Cys Uncertain significance ★ ⚠ same residue
PASK c.3533+1G>A Uncertain significance ★★ same type
PASK p.Arg1319His 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-arg937his (accessed [today's date]).

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