Is PEX1 p.Ala651Thr (c.1951G>A) pathogenic?

PEX1 p.Ala651Thr (c.1951G>A) is classified Uncertain significance in PEX1 (ClinVar, Single submitter, 1 submitter; last evaluated 2018-08-17). AlphaMissense: ambiguous (0.4759); Absent from gnomAD v4.1.

How common is PEX1 p.Ala651Thr (c.1951G>A) in the general population?

PEX1 p.Ala651Thr (c.1951G>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about PEX1 p.Ala651Thr (c.1951G>A)?

AlphaMissense predicts ambiguous (score 0.4759) — an in-silico prediction, not a clinical call.

PEX1 p.Ala651Thr

c.1951G>A · rs1562856189 · VCV598460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4759 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,613,906)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4759	ambiguous
REVEL	0.773	moderately pathogenic-leaning
SaProt	LLR -12.32	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.7	GERP 4.3, phastCons 1
Regional constraint	o/e 0.89	unconstrained · MANE · 41 kb · p 4.3e-05 · regional, not allelic
Overall
CADD	27.0	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 1,613,906). 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: PEX1
Protein: p.Ala651Thr
Coding: c.1951G>A
MANE Select: NM_000466
dbSNP: rs1562856189
Type: single nucleotide variant
Location: chr7:92504852 (GRCh38)
Gene constraint: LOEUF 0.746 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 67.19
Residue 651: a UniProt-annotated variant site (in pbd1a and pbd1b)

Full PEX1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PEX1 c.1239+1G>T Pathogenic ★★ same type
PEX1 c.130-1G>T Pathogenic/Likely pathogenic ★★ same type
PEX1 c.130-2A>G Pathogenic/Likely pathogenic ★★ same type
PEX1 c.130-2A>T Pathogenic/Likely pathogenic ★★ same type
PEX1 c.1483+1G>A Pathogenic ★★ same type
PEX1 c.1587+1G>A Likely pathogenic ★★ same type
PEX1 c.1670+1G>A Pathogenic/Likely pathogenic ★★ same type
PEX1 c.1670+1G>T 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/pex1-p-ala651thr (accessed [today's date]).

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