Is PDCD10 p.Phe76Val (c.226T>G) pathogenic?

PDCD10 p.Phe76Val (c.226T>G) is classified Uncertain significance in PDCD10 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-07). AlphaMissense: likely benign (0.3327); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PDCD10 p.Phe76Val (c.226T>G)?

PDCD10 p.Phe76Val (c.226T>G) is associated with Inborn genetic diseases (ClinVar).

How common is PDCD10 p.Phe76Val (c.226T>G) in the general population?

PDCD10 p.Phe76Val (c.226T>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PDCD10 p.Phe76Val (c.226T>G)?

AlphaMissense predicts likely benign (score 0.3327) — an in-silico prediction, not a clinical call.

PDCD10 p.Phe76Val

c.226T>G · VCV3389690

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.3327 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.3327	likely benign
REVEL	0.387	indeterminate
SaProt	LLR -4.33	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.5, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 36 kb · p 3.1e-06 · regional, not allelic
Overall
CADD	23.1	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: PDCD10
Protein: p.Phe76Val
Coding: c.226T>G
MANE Select: NM_007217
Type: single nucleotide variant
Location: chr3:167697051 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 10 PDB
Residue 76: an α-helix

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

PDCD10 p.Phe76= Likely benign ★★ same residue
PDCD10 p.Asn104Ser Uncertain significance ★★ ⚠ same condition
PDCD10 p.Leu44Arg Uncertain significance ★★ ⚠ same condition
PDCD10 p.Tyr27Cys Uncertain significance ★★ ⚠ same condition
PDCD10 p.Ala46= Likely benign ★★ same condition
PDCD10 p.Phe127= Likely benign ★★ same condition
PDCD10 p.Val72Leu Benign/Likely benign ★★ same condition
PDCD10 p.Asn156Lys Uncertain significance ★ ⚠ same condition

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-phe76val (accessed [today's date]).

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