Is PDCD10 p.Phe191Ile (c.571T>A) pathogenic?

PDCD10 p.Phe191Ile (c.571T>A) is classified Uncertain significance in PDCD10 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-04-24). AlphaMissense: likely pathogenic (0.989); Very rare (popmax 0.000945%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PDCD10 p.Phe191Ile (c.571T>A)?

PDCD10 p.Phe191Ile (c.571T>A) is associated with Inborn genetic diseases (ClinVar).

How common is PDCD10 p.Phe191Ile (c.571T>A) in the general population?

PDCD10 p.Phe191Ile (c.571T>A) is very rare (popmax 0.000945%, nfe) (gnomAD).

What do computational predictors say about PDCD10 p.Phe191Ile (c.571T>A)?

AlphaMissense predicts likely pathogenic (score 0.989) — an in-silico prediction, not a clinical call.

PDCD10 p.Phe191Ile

c.571T>A · rs1307939409 · VCV2539866

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.989 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.000945%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.989	likely pathogenic
REVEL	0.542	indeterminate
SaProt	LLR -6.79	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 11	GERP 2.4, phastCons 1
Regional constraint	o/e 0.71	unconstrained · MANE · 36 kb · p 3.1e-06 · regional, not allelic
Overall
CADD	26.1	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 0.000945% European (non-Finnish) · 11/1,164,216 alleles

Filtering AF 0.000507% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000371%

Overall 0.000689% 11/1,596,272 alleles · very rare

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.Phe191Ile
Coding: c.571T>A
MANE Select: NM_007217
dbSNP: rs1307939409
Type: single nucleotide variant
Location: chr3:167684376 (GRCh38)
Gene constraint: LOEUF 0.924 · pLI 0.64 (gnomAD)
Structure: AlphaFold pLDDT 90.82 · 10 PDB
Residue 191: 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.Phe191= Likely benign ★★ same residue
PDCD10 p.Asn104Ser Uncertain significance ★★ ⚠ same condition
PDCD10 p.Leu44Arg Uncertain significance ★★ ⚠ same condition
PDCD10 p.Phe76Val 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

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-phe191ile (accessed [today's date]).

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