Is THBD p.Ser452= (c.1356C>A) pathogenic?

THBD p.Ser452= (c.1356C>A) is classified Benign/Likely benign in THBD (ClinVar, Multiple submitters, 3 submitters; last evaluated 2025-11-05). Rare (popmax 0.417%, eas); Associated with kidney disorder.

What condition is associated with THBD p.Ser452= (c.1356C>A)?

THBD p.Ser452= (c.1356C>A) is associated with kidney disorder (ClinVar).

How common is THBD p.Ser452= (c.1356C>A) in the general population?

THBD p.Ser452= (c.1356C>A) is rare (popmax 0.417%, eas) (gnomAD).

THBD p.Ser452=

c.1356C>A · rs532533123 · VCV1012478

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

gnomAD v4.1

Rare

rare (popmax 0.417%, eas)

Conditions

kidney disorder

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -2.2	GERP -2.8
Overall
CADD	0.266	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.417% East Asian · 187/44,876 alleles

Filtering AF 0.368% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.349%

Overall 0.0179% 289/1,613,708 alleles · rare exomes 274/1,461,360 · genomes 15/152,348 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.417%	240
South Asian	0.0439%	2,277
Remaining individualsnot grpmax-eligible	0.0128%	7,813
European (non-Finnish)	0.00449%	22,265
Admixed American	0.00167%	60,030

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: THBD
Protein: p.Ser452=
Coding: c.1356C>A
MANE Select: NM_000361
dbSNP: rs532533123
Type: single nucleotide variant
Location: chr20:23048149 (GRCh38)
Gene constraint: LOEUF 1.938 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 79.35 · 13 PDB
Residue 452: the egf-like 6; calcium-binding domain; a β-strand

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

Disease context

kidney disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

THBD p.Ser452Phe Uncertain significance ★ ⚠ same residue
THBD p.Ser452Tyr Uncertain significance ★ ⚠ same residue
THBD p.Asp486Tyr Benign/Likely benign ★★ same condition
THBD p.Ala19= Conflicting classifications of pathogenicity ★ same condition
THBD p.Cys537Ter Pathogenic/Likely pathogenic ★★ same type
THBD p.Ala139Ser Uncertain significance ★★ ⚠ same type
THBD p.Ala21Ser Uncertain significance ★★ ⚠ same type
THBD p.Ala255Pro 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/thbd-p-ser452 (accessed [today's date]).

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