Is PEX3 p.Ser71Phe (c.212C>T) pathogenic?

PEX3 p.Ser71Phe (c.212C>T) is classified Uncertain significance in PEX3 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-03-26). AlphaMissense: likely pathogenic (0.8997); Ultra-rare (popmax 0.0308%, sas).

How common is PEX3 p.Ser71Phe (c.212C>T) in the general population?

PEX3 p.Ser71Phe (c.212C>T) is ultra-rare (popmax 0.0308%, sas) (gnomAD).

What do computational predictors say about PEX3 p.Ser71Phe (c.212C>T)?

AlphaMissense predicts likely pathogenic (score 0.8997) — an in-silico prediction, not a clinical call.

PEX3 p.Ser71Phe

c.212C>T · rs561349643 · VCV1387168

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8997 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0308%, sas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Computational evidence

Protein change
AlphaMissense	0.8997	likely pathogenic
REVEL	0.613	indeterminate
SaProt	LLR -14.40	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.81	unconstrained · MANE · 38 kb · p 8.4e-05 · regional, not allelic
Overall
CADD	31.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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

Grpmax group 0.0308% South Asian · 28/91,036 alleles

Filtering AF 0.0218% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0188%

Overall 0.00174% 28/1,611,938 alleles · ultra-rare exomes 26/1,459,752 · genomes 2/152,186 · 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: PEX3
Protein: p.Ser71Phe
Coding: c.212C>T
MANE Select: NM_003630
dbSNP: rs561349643
Type: single nucleotide variant
Location: chr6:143462922 (GRCh38)
Gene constraint: LOEUF 0.972 · pLI 0.12 (gnomAD)
Structure: AlphaFold pLDDT 88.94 · 2 PDB
Residue 71: an α-helix

Full PEX3 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PEX3 c.288-1G>A Pathogenic/Likely pathogenic ★★ same type
PEX3 c.942-1G>T Likely pathogenic ★★ same type
PEX3 p.Arg256Ter Pathogenic/Likely pathogenic ★★ same type
PEX3 p.Arg286Ter Pathogenic ★★ same type
PEX3 p.Trp6Ter Pathogenic ★★ same type
PEX3 c.818+3A>G Uncertain significance ★★ same type
PEX3 c.-96G>T Uncertain significance ★★ same type
PEX3 p.Ala358Val 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/pex3-p-ser71phe (accessed [today's date]).

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