Is PASK p.Ser71Phe (c.212C>T) pathogenic?

PASK p.Ser71Phe (c.212C>T) is classified Likely benign in PASK (ClinVar, Single submitter, 1 submitter; last evaluated 2018-11-20). AlphaMissense: ambiguous (0.3416); Rare (popmax 0.724%, afr).

How common is PASK p.Ser71Phe (c.212C>T) in the general population?

PASK p.Ser71Phe (c.212C>T) is rare (popmax 0.724%, afr) (gnomAD).

What do computational predictors say about PASK p.Ser71Phe (c.212C>T)?

AlphaMissense predicts ambiguous (score 0.3416) — an in-silico prediction, not a clinical call.

PASK p.Ser71Phe

c.212C>T · rs148125949 · VCV791903

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3416 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.724%, afr)

Computational evidence

Protein change
AlphaMissense	0.3416	ambiguous
REVEL	0.441	indeterminate
SaProt	LLR -8.08	tolerated
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.6	GERP 1.2, phastCons 1
Regional constraint	o/e 1.01	unconstrained · MANE · 17 kb · p 0.68 · regional, not allelic
Overall
CADD	24.9	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 0.724% African / African-American · 543/74,984 alleles

Filtering AF 0.674% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.654%

Overall 0.0363% 585/1,609,936 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.724%	138
Remaining individualsnot grpmax-eligible	0.0337%	2,970
Admixed American	0.0317%	3,159
South Asian	0.0011%	90,994
European (non-Finnish)	8.5e-05%	1,176,172

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.Ser71Phe
Coding: c.212C>T
MANE Select: NM_015148
dbSNP: rs148125949
Type: single nucleotide variant
Location: chr2:241140738 (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-ser71phe (accessed [today's date]).

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