Is PLAT p.Asp167= (c.501C>T) pathogenic?

PLAT p.Asp167= (c.501C>T) is classified Benign in PLAT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-09-29). Common (popmax 57.3%, nfe) — too common for a highly-penetrant pathogenic allele.

PLAT p.Asp167=

Q: How common is PLAT p.Asp167= (c.501C>T) in the general population?

PLAT p.Asp167= (c.501C>T) is common (popmax 57.3%, nfe) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.501C>T · VCV4683338

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Common

common (popmax 57.3%, nfe) — too common for a highly-penetrant pathogenic allele

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -3.6	GERP -3.5
Overall
CADD	0.073	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 57.3% European (non-Finnish) · 674,714/1,177,472 alleles

Filtering AF 57.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 57.1%

Overall 56% 896,578/1,599,912 alleles · common exomes 818,148/1,447,684 · genomes 78,430/152,228 · joint denominator

Ancestry group	Frequency	1 in
Finnishnot grpmax-eligible	58%	2
European (non-Finnish)grpmax	57.3%	2
Admixed American	56.9%	2
South Asian	55.5%	2
Remaining individualsnot grpmax-eligible	55.4%	2
Amishnot grpmax-eligible	54.9%	2
East Asian	54.4%	2
Ashkenazi Jewishnot grpmax-eligible	49.5%	2
Middle Eastern	48.3%	2
African / African-American	39.5%	3

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: PLAT
Protein: p.Asp167=
Coding: c.501C>T
MANE Select: NM_000930
Type: single nucleotide variant
Location: chr8:42187436 (GRCh38)
Gene constraint: LOEUF 0.804 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.28 · 11 PDB
Residue 167: the kringle 1 domain

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

Similar variants

PLAT p.Arg184Gly Uncertain significance ★★ ⚠ same type
PLAT p.Val280Met Uncertain significance ★★ ⚠ same type
PLAT p.Ala34Asp Likely benign ★★ same type
PLAT p.Ala493= Benign/Likely benign ★★ same type
PLAT p.Arg561Ter Benign ★★ same type
PLAT p.Pro543= Likely benign ★★ same type
PLAT p.Ser154= Likely benign ★★ same type
PLAT p.Ser513= 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/plat-p-asp167 (accessed [today's date]).

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