Is PASK p.Val694Met (c.2080G>A) pathogenic?

PASK p.Val694Met (c.2080G>A) is classified Benign in PASK (ClinVar, Multiple submitters, 2 submitters; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1026); Common (popmax 8.38%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about PASK p.Val694Met (c.2080G>A)?

AlphaMissense predicts likely benign (score 0.1026) — an in-silico prediction, not a clinical call.

PASK p.Val694Met

Q: How common is PASK p.Val694Met (c.2080G>A) in the general population?

PASK p.Val694Met (c.2080G>A) is common (popmax 8.38%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.2080G>A · rs6727226 · VCV788220

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.1026 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 8.38%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1026	likely benign
REVEL	0.114	moderately benign-leaning
SaProt	LLR -8.35	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 -1.9	GERP -2.6
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.68 · regional, not allelic
Overall
CADD	1.475	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 8.38% African / African-American · 6,288/75,012 alleles

Filtering AF 8.21% ClinGen BA1/BS1 input FAF95, joint · FAF99 8.14%

Overall 0.468% 7,547/1,613,096 alleles · common exomes 3,834/1,460,748 · genomes 3,713/152,348 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	8.38%	12
Remaining individualsnot grpmax-eligible	0.647%	155
Admixed American	0.57%	175
Middle Eastern	0.561%	178
European (non-Finnish)	0.0393%	2,541
South Asian	0.0165%	6,071

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.Val694Met
Coding: c.2080G>A
MANE Select: NM_015148
dbSNP: rs6727226
Type: single nucleotide variant
Location: chr2:241126835 (GRCh38)
Gene constraint: LOEUF 1.03 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 54.14 · 2 PDB
Residue 694: a UniProt-annotated variant site (in)

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-val694met (accessed [today's date]).

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