Is PDAP1 p.Ala130Ser (c.388G>T) pathogenic?

PDAP1 p.Ala130Ser (c.388G>T) is classified Uncertain significance in PDAP1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-24). AlphaMissense: ambiguous (0.4993); Very rare (popmax 0.00432%, nfe).

How common is PDAP1 p.Ala130Ser (c.388G>T) in the general population?

PDAP1 p.Ala130Ser (c.388G>T) is very rare (popmax 0.00432%, nfe) (gnomAD).

What do computational predictors say about PDAP1 p.Ala130Ser (c.388G>T)?

AlphaMissense predicts ambiguous (score 0.4993) — an in-silico prediction, not a clinical call.

PDAP1 p.Ala130Ser

c.388G>T · rs779765406 · VCV2513277

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4993 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4993	ambiguous
REVEL	0.178	moderately benign-leaning
SaProt	LLR -7.91	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 1.6, phastCons 1
Regional constraint	o/e 0.65	unconstrained · MANE · 12 kb · p 1.3e-07 · regional, not allelic
Overall
CADD	26.6	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 0.00432% European (non-Finnish) · 51/1,180,050 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00316% 51/1,614,148 alleles · very rare exomes 48/1,461,866 · genomes 3/152,282 · joint denominator

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.Ala130Ser
Coding: c.388G>T
MANE Select: NM_014891
dbSNP: rs779765406
Type: single nucleotide variant
Location: chr7:99397961 (GRCh38)
Gene constraint: LOEUF 0.934 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.09

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

Similar variants

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
PDAP1 p.Glu152Ala 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-ala130ser (accessed [today's date]).

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