Is PEX6 p.Ala978Pro (c.2932G>C) pathogenic?

PEX6 p.Ala978Pro (c.2932G>C) is classified Uncertain significance in PEX6 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-08). AlphaMissense: likely benign (0.171); Very rare (popmax 8.47e-05%, nfe); Associated with Inborn genetic diseases.

What condition is associated with PEX6 p.Ala978Pro (c.2932G>C)?

PEX6 p.Ala978Pro (c.2932G>C) is associated with Inborn genetic diseases (ClinVar).

How common is PEX6 p.Ala978Pro (c.2932G>C) in the general population?

PEX6 p.Ala978Pro (c.2932G>C) is very rare (popmax 8.47e-05%, nfe) (gnomAD).

What do computational predictors say about PEX6 p.Ala978Pro (c.2932G>C)?

AlphaMissense predicts likely benign (score 0.171) — an in-silico prediction, not a clinical call.

PEX6 p.Ala978Pro

c.2932G>C · VCV4134936

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.171 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.47e-05%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.171	likely benign
REVEL	0.558	indeterminate
SaProt	LLR -10.99	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4	GERP 1.7, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 4,158 bp · p 6.4e-06 · regional, not allelic
Overall
CADD	25.4	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 8.47e-05% European (non-Finnish) · 1/1,179,988 alleles

Overall 6.2e-05% 1/1,613,742 alleles · very rare exomes 1/1,461,394 · genomes 0/152,348 · 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: PEX6
Protein: p.Ala978Pro
Coding: c.2932G>C
MANE Select: NM_000287
Type: single nucleotide variant
Location: chr6:42964346 (GRCh38)
Gene constraint: LOEUF 0.799 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 69.87

Full PEX6 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

PEX6 p.Ala978= Likely benign ★★ same residue
PEX6 p.Ala240Gly Uncertain significance ★★ ⚠ same condition
PEX6 p.Ala2Thr Uncertain significance ★★ ⚠ same condition
PEX6 p.Ala51Glu Uncertain significance ★★ ⚠ same condition
PEX6 p.Ala581Thr Uncertain significance ★★ ⚠ same condition
PEX6 p.Arg209Trp Uncertain significance ★★ ⚠ same condition
PEX6 p.Arg229Lys Uncertain significance ★★ ⚠ same condition
PEX6 p.Arg469Gln 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/pex6-p-ala978pro (accessed [today's date]).

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