Is PDAP1 p.Val96Phe (c.286G>T) pathogenic?

PDAP1 p.Val96Phe (c.286G>T) is classified Uncertain significance in PDAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-06). AlphaMissense: likely pathogenic (0.7217); Very rare (popmax 0.00805%, nfe).

How common is PDAP1 p.Val96Phe (c.286G>T) in the general population?

PDAP1 p.Val96Phe (c.286G>T) is very rare (popmax 0.00805%, nfe) (gnomAD).

What do computational predictors say about PDAP1 p.Val96Phe (c.286G>T)?

AlphaMissense predicts likely pathogenic (score 0.7217) — an in-silico prediction, not a clinical call.

PDAP1 p.Val96Phe

c.286G>T · rs376528383 · VCV2381375

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.7217 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00805%, nfe)

Missense predictors

2/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.7217	likely pathogenic
REVEL	0.137	moderately benign-leaning
SaProt	LLR -13.19	damaging
⇒ AlphaMissense and SaProt call this damaging; REVEL does not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 12 kb · p 1.3e-07 · regional, not allelic
Overall
CADD	24.4	PHRED · no single calibrated threshold — expert panels disagree

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

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00805% European (non-Finnish) · 95/1,179,908 alleles

Filtering AF 0.00672% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00624%

Overall 0.00706% 114/1,613,892 alleles · very rare exomes 109/1,461,698 · genomes 5/152,194 · joint denominator

Ancestry group	Frequency	1 in
Remaining individualsnot grpmax-eligible	0.0192%	5,206
European (non-Finnish)grpmax	0.00805%	12,420
South Asian	0.00549%	18,217
Admixed American	0.00167%	59,992
African / African-American	0.00133%	74,912

Remaining individuals 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: PDAP1
Protein: p.Val96Phe
Coding: c.286G>T
MANE Select: NM_014891
dbSNP: rs376528383
Type: single nucleotide variant
Location: chr7:99400352 (GRCh38)
Gene constraint: LOEUF 0.934 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.09
Residue 96: the 'disordered' region

Full PDAP1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDAP1 p.Ala130Ser Uncertain significance ★ ⚠ same type
PDAP1 p.Ala144Thr Uncertain significance ★ ⚠ same type
PDAP1 p.Ala14Val Uncertain significance ★ ⚠ same type
PDAP1 p.Ala167Ser Uncertain significance ★ ⚠ same type
PDAP1 p.Asn180His Uncertain significance ★ ⚠ same type
PDAP1 p.Asp166Asn Uncertain significance ★ ⚠ same type
PDAP1 p.Asp24Asn Uncertain significance ★ ⚠ same type
PDAP1 p.Glu106Ala 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/pdap1-p-val96phe (accessed [today's date]).

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