Is PDF p.Thr96Met (c.287C>T) pathogenic?

PDF p.Thr96Met (c.287C>T) is classified Uncertain significance in PDF (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-31). AlphaMissense: likely benign (0.1138); Very rare (popmax 0.00899%, afr).

How common is PDF p.Thr96Met (c.287C>T) in the general population?

PDF p.Thr96Met (c.287C>T) is very rare (popmax 0.00899%, afr) (gnomAD).

What do computational predictors say about PDF p.Thr96Met (c.287C>T)?

AlphaMissense predicts likely benign (score 0.1138) — an in-silico prediction, not a clinical call.

PDF p.Thr96Met

c.287C>T · rs976129216 · VCV2309923

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1138 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00899%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1138	likely benign
REVEL	0.083	moderately benign-leaning
SaProt	LLR -8.38	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not looked up on this page · why
Constraint at this position
Conservation	phyloP 3.9	GERP 0.58, phastCons 1
Regional constraint	o/e 1.23	unconstrained · MANE · 1,545 bp · p 9e-06 · regional, not allelic
Overall
CADD	17.74	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00899% African / African-American · 6/66,712 alleles

Filtering AF 0.00382% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00262%

Overall 0.00119% 17/1,431,794 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00899%	11,119
South Asian	0.00711%	14,064
East Asian	0.00303%	33,054
European (non-Finnish)	0.000454%	220,401

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.Thr96Met
Coding: c.287C>T
MANE Select: NM_032382 · reported on NM_022341
dbSNP: rs976129216
Type: single nucleotide variant
Location: chr16:69330284 (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-thr96met (accessed [today's date]).

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