Is PDCD10 p.Ala85Val (c.254C>T) pathogenic?

PDCD10 p.Ala85Val (c.254C>T) is classified Uncertain significance in PDCD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-01). AlphaMissense: ambiguous (0.378); Very rare (popmax 0.00032%).

How common is PDCD10 p.Ala85Val (c.254C>T) in the general population?

PDCD10 p.Ala85Val (c.254C>T) is very rare (popmax 0.00032%) (gnomAD).

What do computational predictors say about PDCD10 p.Ala85Val (c.254C>T)?

AlphaMissense predicts ambiguous (score 0.378) — an in-silico prediction, not a clinical call.

PDCD10 p.Ala85Val

c.254C>T · rs1218260194 · VCV3025829

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.378 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00032%)

Computational evidence

Protein change
AlphaMissense	0.378	ambiguous
REVEL	0.328	indeterminate
SaProt	LLR -9.12	tolerated
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>C here scores Δ0.42 · evaluated, not missing
Constraint at this position
Conservation	phyloP 12	GERP 2.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 36 kb · p 3.1e-06 · regional, not allelic
Overall
CADD	26.2	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 0.00032%

Overall 0.00032% 5/1,561,636 alleles · very rare exomes 5/1,409,362 · genomes 0/152,274 · 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: PDCD10
Protein: p.Ala85Val
Coding: c.254C>T
MANE Select: NM_007217
dbSNP: rs1218260194
Type: single nucleotide variant
Location: chr3:167697023 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 10 PDB
Residue 85: a turn

Full PDCD10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PDCD10 c.150+1G>A Pathogenic/Likely pathogenic ★★ same type
PDCD10 c.268+1G>A Pathogenic ★★ same type
PDCD10 c.396-2A>G Pathogenic ★★ same type
PDCD10 c.474+5G>A Pathogenic/Likely pathogenic ★★ same type
PDCD10 c.557+1G>A Pathogenic ★★ same type
PDCD10 p.Arg108Ter Pathogenic ★★ same type
PDCD10 p.Arg196Ter Pathogenic ★★ same type
PDCD10 p.Arg35Ter Pathogenic ★★ 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/pdcd10-p-ala85val (accessed [today's date]).

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