Is STUB1 p.Phe131= (c.393C>T) pathogenic?

STUB1 p.Phe131= (c.393C>T) is classified Likely benign in STUB1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-13). Very rare (popmax 0.00729%, nfe).

How common is STUB1 p.Phe131= (c.393C>T) in the general population?

STUB1 p.Phe131= (c.393C>T) is very rare (popmax 0.00729%, nfe) (gnomAD).

STUB1 p.Phe131=

c.393C>T · rs143361117 · VCV1943947

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00729%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -1	GERP -4.4, phastCons 0.004
Overall
CADD	15.98	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00729% European (non-Finnish) · 86/1,179,884 alleles

Filtering AF 0.00604% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00557%

Overall 0.00583% 94/1,612,510 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0101%	9,867
European (non-Finnish)grpmax	0.00729%	13,720
Remaining individualsnot grpmax-eligible	0.0048%	20,819
Admixed American	0.00167%	59,994
South Asian	0.0011%	91,068

Ashkenazi Jewish 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: STUB1
Protein: p.Phe131=
Coding: c.393C>T
MANE Select: NM_005861
dbSNP: rs143361117
Type: single nucleotide variant
Location: chr16:681472 (GRCh38)
Gene constraint: LOEUF 1.294 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 89.84 · 27 PDB
Residue 131: the 'required for interaction with mapk7' region

Full STUB1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

STUB1 p.Phe131Leu Uncertain significance ★ ⚠ same residue
STUB1 p.Asn65Ser Pathogenic/Likely pathogenic ★★ same type
STUB1 p.Tyr49Cys Pathogenic/Likely pathogenic ★★ ⚠ same type
STUB1 p.Ala11Thr Uncertain significance ★★ ⚠ same type
STUB1 p.Arg173Leu Uncertain significance ★★ ⚠ same type
STUB1 p.Arg35Pro Uncertain significance ★★ ⚠ same type
STUB1 p.Asn34Ser Uncertain significance ★★ ⚠ same type
STUB1 p.Cys48Tyr Uncertain significance ★★ ⚠ 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/stub1-p-phe131 (accessed [today's date]).

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