Is PCCA p.Pro554Arg (c.1661C>G) pathogenic?

PCCA p.Pro554Arg (c.1661C>G) is classified Uncertain significance in PCCA (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-29). AlphaMissense: likely benign (0.0885); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with PCCA p.Pro554Arg (c.1661C>G)?

PCCA p.Pro554Arg (c.1661C>G) is associated with Inborn genetic diseases (ClinVar).

How common is PCCA p.Pro554Arg (c.1661C>G) in the general population?

PCCA p.Pro554Arg (c.1661C>G) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PCCA p.Pro554Arg (c.1661C>G)?

AlphaMissense predicts likely benign (score 0.0885) — an in-silico prediction, not a clinical call.

PCCA p.Pro554Arg

c.1661C>G · VCV3414669

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0885 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.0885	likely benign
REVEL	0.252	benign-leaning
SaProt	LLR -5.80	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 2.7	GERP 0.35, phastCons 0.038
Regional constraint	o/e 0.98	unconstrained · MANE · 441 kb · p 0.59 · regional, not allelic
Overall
CADD	12.61	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: PCCA
Protein: p.Pro554Arg
Coding: c.1661C>G
MANE Select: NM_000282
Type: single nucleotide variant
Location: chr13:100368489 (GRCh38)
Gene constraint: LOEUF 0.986 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 87.56 · 26 PDB

Full PCCA 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

PCCA p.Pro554Ala Uncertain significance ⚠ same residue
PCCA c.915-1G>C Pathogenic/Likely pathogenic ★★ same condition
PCCA p.Ala2Pro Uncertain significance ★★ ⚠ same condition
PCCA p.Ala310Val Uncertain significance ★★ ⚠ same condition
PCCA p.Ala701Pro Uncertain significance ★★ ⚠ same condition
PCCA p.Arg268His Uncertain significance ★★ ⚠ same condition
PCCA p.Arg430Gln Uncertain significance ★★ ⚠ same condition
PCCA p.Arg486Gln 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/pcca-p-pro554arg (accessed [today's date]).

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