Is PDF p.Arg164= (c.492C>T) pathogenic?

PDF p.Arg164= (c.492C>T) is classified Benign in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2026-06-01). Low-frequency (popmax 1.35%, nfe).

How common is PDF p.Arg164= (c.492C>T) in the general population?

PDF p.Arg164= (c.492C>T) is low-frequency (popmax 1.35%, nfe) (gnomAD).

PDF p.Arg164=

c.492C>T · rs138307515 · VCV2646672

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

low-frequency (popmax 1.35%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 1.5	GERP -1.5, phastCons 1
Overall
CADD	10.88	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 1.35% European (non-Finnish) · 15,705/1,160,184 alleles

Filtering AF 1.34% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.33%

Overall 1.13% 17,675/1,570,000 alleles · low-frequency

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	1.36%	74
European (non-Finnish)grpmax	1.35%	74
Admixed American	1.03%	97
Remaining individualsnot grpmax-eligible	1%	100
Amishnot grpmax-eligible	0.439%	228
Finnishnot grpmax-eligible	0.351%	285
African / African-American	0.223%	448
Middle Eastern	0.202%	495
South Asian	0.0268%	3,729

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: PDF
Protein: p.Arg164=
Coding: c.492C>T
MANE Select: NM_032382 · reported on NM_022341
dbSNP: rs138307515
Type: single nucleotide variant
Location: chr16:69330079 (GRCh38)

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

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/pdf-p-arg164 (accessed [today's date]).

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