Is PABPC4 p.Pro560Ala (c.1678C>G) pathogenic?

PABPC4 p.Pro560Ala (c.1678C>G) is classified Uncertain significance in PABPC4 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-07). AlphaMissense: likely benign (0.0775); Very rare (popmax 0.00212%, nfe).

How common is PABPC4 p.Pro560Ala (c.1678C>G) in the general population?

PABPC4 p.Pro560Ala (c.1678C>G) is very rare (popmax 0.00212%, nfe) (gnomAD).

What do computational predictors say about PABPC4 p.Pro560Ala (c.1678C>G)?

AlphaMissense predicts likely benign (score 0.0775) — an in-silico prediction, not a clinical call.

PABPC4 p.Pro560Ala

c.1678C>G · rs777556247 · VCV2265624

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0775 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00212%, nfe)

Missense predictors

0/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.0775	likely benign
REVEL	0.443	indeterminate
SaProt	LLR -8.63	tolerated
⇒ AlphaMissense and SaProt both call this tolerated; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 3,055 bp · p 0.15 · regional, not allelic
Overall
CADD	24.9	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.

⚠ Isoform check: AlphaMissense numbered on a different transcript (AM P544A vs ClinVar P560A) — verify the residue.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00212% European (non-Finnish) · 25/1,179,664 alleles

Filtering AF 0.00145% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00123%

Overall 0.00155% 25/1,613,190 alleles · very rare exomes 21/1,460,988 · genomes 4/152,202 · 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: PABPC4
Protein: p.Pro560Ala
Coding: c.1678C>G
MANE Select: NM_001135653
dbSNP: rs777556247
Type: single nucleotide variant
Location: chr1:39562407 (GRCh38)
Gene constraint: LOEUF 0.311 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 76.70

Full PABPC4 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PABPC4 p.Ala34Ser Uncertain significance ★ ⚠ same type
PABPC4 p.Ala523Ser Uncertain significance ★ ⚠ same type
PABPC4 p.Ala523Val Uncertain significance ★ ⚠ same type
PABPC4 p.Ala526Thr Uncertain significance ★ ⚠ same type
PABPC4 p.Ala542Val Uncertain significance ★ ⚠ same type
PABPC4 p.Ala654Val Uncertain significance ★ ⚠ same type
PABPC4 p.Arg166Cys Uncertain significance ★ ⚠ same type
PABPC4 p.Arg176His Uncertain significance ★ ⚠ 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/pabpc4-p-pro560ala (accessed [today's date]).

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