Is PEX6 p.Ser77Arg (c.231C>A) pathogenic?

PEX6 p.Ser77Arg (c.231C>A) is classified Uncertain significance in PEX6 (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.8238); No allele count reported in gnomAD v4.1 (AN 1,488,552); Associated with peroxisome biogenesis disorder 4A (Zellweger).

What condition is associated with PEX6 p.Ser77Arg (c.231C>A)?

PEX6 p.Ser77Arg (c.231C>A) is associated with peroxisome biogenesis disorder 4A (Zellweger), peroxisome biogenesis disorder 4B (ClinVar).

How common is PEX6 p.Ser77Arg (c.231C>A) in the general population?

PEX6 p.Ser77Arg (c.231C>A) is no allele count reported in gnomAD v4.1 (AN 1,488,552) (gnomAD).

What do computational predictors say about PEX6 p.Ser77Arg (c.231C>A)?

AlphaMissense predicts likely pathogenic (score 0.8238) — an in-silico prediction, not a clinical call.

PEX6 p.Ser77Arg

c.231C>A · rs1770437263 · VCV917829

Uncertain significance No assertion criteria

Classification

Uncertain significance

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8238 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,488,552)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

peroxisome biogenesis disorder 4A (Zellweger)

Computational evidence

Protein change
AlphaMissense	0.8238	likely pathogenic
REVEL	0.171	moderately benign-leaning
SaProt	LLR -8.10	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 7.1	GERP 0.5, phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 10 kb · p 0.19 · regional, not allelic
Overall
CADD	23.0	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

No allele count reported in gnomAD v4.1 (AN 1,488,552). 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: PEX6
Protein: p.Ser77Arg
Coding: c.231C>A
MANE Select: NM_000287
dbSNP: rs1770437263
Type: single nucleotide variant
Location: chr6:42978920 (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

peroxisome biogenesis disorder 4A (Zellweger) — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: peroxisome biogenesis disorder 4B

Similar variants

PEX6 c.1130+1G>A Likely pathogenic ★★ same condition
PEX6 c.1233+1G>A Likely pathogenic ★★ same condition
PEX6 c.1688+1G>A Pathogenic ★★ same condition
PEX6 c.1689-1G>A Likely pathogenic ★★ same condition
PEX6 c.1961+1G>A Likely pathogenic ★★ same condition
PEX6 c.1962-1G>A Pathogenic/Likely pathogenic ★★ same condition
PEX6 c.2362+1G>A Likely pathogenic ★★ same condition
PEX6 c.882+1G>A Pathogenic/Likely pathogenic ★★ 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-ser77arg (accessed [today's date]).

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