Is PAX8 p.Ser337= (c.1011C>T) pathogenic?

PAX8 p.Ser337= (c.1011C>T) is classified Likely benign in PAX8 (ClinVar, Single submitter, 1 submitter; last evaluated 2017-06-29). Ultra-rare (popmax 0.0156%, eas).

How common is PAX8 p.Ser337= (c.1011C>T) in the general population?

PAX8 p.Ser337= (c.1011C>T) is ultra-rare (popmax 0.0156%, eas) (gnomAD).

PAX8 p.Ser337=

c.1011C>T · rs1553412951 · VCV518071

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0156%, eas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
REVEL	0.292	indeterminate
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 3.5	GERP -3.2, phastCons 1
Overall
CADD	14.34	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0156% East Asian · 7/44,854 alleles

Filtering AF 0.00726% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00515%

Overall 0.000496% 8/1,613,044 alleles · ultra-rare exomes 8/1,460,730 · genomes 0/152,314 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0156%	6,408
Finnishnot grpmax-eligible	0.00156%	63,936

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: PAX8
Protein: p.Ser337=
Coding: c.1011C>T
MANE Select: NM_003466
dbSNP: rs1553412951
Type: single nucleotide variant
Location: chr2:113235470 (GRCh38)
Gene constraint: LOEUF 0.415 · pLI 1.00 · ClinGen HI 1/3 (gnomAD)
Structure: AlphaFold pLDDT 58.09 · 1 PDB

Full PAX8 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

PAX8 p.Ser337Ala Conflicting classifications of pathogenicity ★ ⚠ same residue
PAX8 p.Arg133Gln Pathogenic/Likely pathogenic ★★ same type
PAX8 c.*1765G>A Uncertain significance ★★ same type
PAX8 c.*290G>A Uncertain significance ★★ same type
PAX8 c.*845G>A Uncertain significance ★★ same type
PAX8 p.Gln354Glu Uncertain significance ★★ ⚠ same type
PAX8 p.Gly11Arg Uncertain significance ★★ ⚠ same type
PAX8 p.Leu266Ser 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/pax8-p-ser337 (accessed [today's date]).

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