Is VPS13C p.Phe142= (c.426T>C) pathogenic?

VPS13C p.Phe142= (c.426T>C) is classified Likely benign in VPS13C (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-10-31). Ultra-rare (popmax 0.0967%, sas).

How common is VPS13C p.Phe142= (c.426T>C) in the general population?

VPS13C p.Phe142= (c.426T>C) is ultra-rare (popmax 0.0967%, sas) (gnomAD).

VPS13C p.Phe142=

c.426T>C · rs144525924 · VCV788740

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0967%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation/SpliceAI carries the signal.
Splicing
SpliceAI	Δ0.36	donor gain · deltas
Constraint at this position
Conservation	phyloP 1.7	GERP -2.6, phastCons 1
Overall
CADD	18.15	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0967% South Asian · 88/91,038 alleles

Filtering AF 0.0803% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0743%

Overall 0.0575% 927/1,613,054 alleles · ultra-rare exomes 867/1,460,848 · genomes 60/152,206 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	0.123%	810
South Asiangrpmax	0.0967%	1,035
Middle Eastern	0.0826%	1,211
European (non-Finnish)	0.0606%	1,649
Remaining individualsnot grpmax-eligible	0.0384%	2,602
African / African-American	0.012%	8,326
Admixed American	0.0117%	8,569

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: VPS13C
Protein: p.Phe142=
Coding: c.426T>C
MANE Select: NM_020821
dbSNP: rs144525924
Type: single nucleotide variant
Location: chr15:62028380 (GRCh38)
Gene constraint: LOEUF 0.857 · pLI <0.01 (gnomAD)

Full VPS13C gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

VPS13C c.5868+1G>A Likely pathogenic ★★ same type
VPS13C p.Arg2936Ter Pathogenic/Likely pathogenic ★★ same type
VPS13C p.Arg3652Ter Pathogenic/Likely pathogenic ★★ same type
VPS13C p.Arg371Ter Pathogenic/Likely pathogenic ★★ same type
VPS13C p.Arg567Ter Pathogenic/Likely pathogenic ★★ same type
VPS13C p.Gln3257Ter Pathogenic ★★ same type
VPS13C p.Glu3354Ter Pathogenic ★★ same type
VPS13C p.Glu3407Ter Pathogenic/Likely pathogenic ★★ 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/vps13c-p-phe142 (accessed [today's date]).

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