Is THBD p.Pro196= (c.588G>T) pathogenic?

THBD p.Pro196= (c.588G>T) is classified Uncertain significance in THBD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-09-04). Ultra-rare (popmax 0.0222%, eas).

How common is THBD p.Pro196= (c.588G>T) in the general population?

THBD p.Pro196= (c.588G>T) is ultra-rare (popmax 0.0222%, eas) (gnomAD).

THBD p.Pro196=

c.588G>T · VCV3603602

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0222%, eas)

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 -2.9	GERP -0.53
Overall
CADD	5.021	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0222% East Asian · 9/40,534 alleles

Filtering AF 0.0115% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00862%

Overall 0.00341% 52/1,526,814 alleles · ultra-rare exomes 50/1,374,640 · genomes 2/152,174 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0222%	4,504
European (non-Finnish)	0.00377%	26,503

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.Pro196=
Coding: c.588G>T
MANE Select: NM_000361
Type: single nucleotide variant
Location: chr20:23048917 (GRCh38)
Gene constraint: LOEUF 1.938 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 79.35 · 13 PDB

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

Similar variants

THBD p.Pro196Arg Uncertain significance ★ same residue
THBD p.Pro196Leu Uncertain significance ★ same residue
THBD p.Pro196Ser Uncertain significance ★ same residue
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
THBD p.Ala271Thr 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-pro196 (accessed [today's date]).

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