Is PPFIA3 p.Pro571Ser (c.1711C>T) pathogenic?

PPFIA3 p.Pro571Ser (c.1711C>T) is classified Uncertain significance in PPFIA3 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-16). AlphaMissense: likely benign (0.0678); No allele count reported in gnomAD v4.1 (AN 1,582,316).

How common is PPFIA3 p.Pro571Ser (c.1711C>T) in the general population?

PPFIA3 p.Pro571Ser (c.1711C>T) is no allele count reported in gnomAD v4.1 (AN 1,582,316) (gnomAD).

What do computational predictors say about PPFIA3 p.Pro571Ser (c.1711C>T)?

AlphaMissense predicts likely benign (score 0.0678) — an in-silico prediction, not a clinical call.

PPFIA3 p.Pro571Ser

c.1711C>T · VCV4721525

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0678 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,582,316)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0678	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.75	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 2.8	phastCons 0.99
Regional constraint	o/e 0.88	unconstrained · MANE · 1,972 bp · p 0.14 · regional, not allelic
Overall
CADD	20.4	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

No allele count reported in gnomAD v4.1 (AN 1,582,316). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: PPFIA3
Protein: p.Pro571Ser
Coding: c.1711C>T
MANE Select: NM_003660
Type: single nucleotide variant
Location: chr19:49136769 (GRCh38)
Gene constraint: LOEUF 0.264 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 70.27
Residue 571: the 'disordered' region

Full PPFIA3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PPFIA3 p.Pro571Leu Uncertain significance ★ ⚠ same residue
PPFIA3 p.Arg415Trp Pathogenic/Likely pathogenic ★★ ⚠ same type
PPFIA3 p.Arg778Ter Pathogenic ★★ same type
PPFIA3 p.Ser906Leu Pathogenic/Likely pathogenic ★★ ⚠ same type
PPFIA3 p.Arg830Cys Uncertain significance ★★ ⚠ same type
PPFIA3 p.Pro802Leu Uncertain significance ★★ ⚠ same type
PPFIA3 p.Ala563Ser Benign ★★ same type
PPFIA3 c.241-1G>A Likely 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/ppfia3-p-pro571ser (accessed [today's date]).

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