Is THBD p.Phe197Val (c.589T>G) pathogenic?

THBD p.Phe197Val (c.589T>G) is classified Uncertain significance in THBD (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-30). AlphaMissense: likely pathogenic (0.8704); No allele count reported in gnomAD v4.1 (AN 1,526,836); Associated with Inborn genetic diseases.

What condition is associated with THBD p.Phe197Val (c.589T>G)?

THBD p.Phe197Val (c.589T>G) is associated with Inborn genetic diseases (ClinVar).

How common is THBD p.Phe197Val (c.589T>G) in the general population?

THBD p.Phe197Val (c.589T>G) is no allele count reported in gnomAD v4.1 (AN 1,526,836) (gnomAD).

What do computational predictors say about THBD p.Phe197Val (c.589T>G)?

AlphaMissense predicts likely pathogenic (score 0.8704) — an in-silico prediction, not a clinical call.

THBD p.Phe197Val

c.589T>G · rs767463897 · VCV3176944

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8704 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,526,836)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.8704	likely pathogenic
REVEL	0.506	indeterminate
SaProt	LLR -6.70	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not; REVEL is indeterminate.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.1	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,724 bp · p 0.25 · regional, not allelic
Overall
CADD	23.6	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 1,526,836). 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: THBD
Protein: p.Phe197Val
Coding: c.589T>G
MANE Select: NM_000361
dbSNP: rs767463897
Type: single nucleotide variant
Location: chr20:23048916 (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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

THBD p.Phe197= Likely benign ★★ same residue
THBD p.Ala21Ser Uncertain significance ★★ ⚠ same condition
THBD p.Ala255Pro Uncertain significance ★★ ⚠ same condition
THBD p.Ala272Val Uncertain significance ★★ ⚠ same condition
THBD p.Arg264His Uncertain significance ★★ ⚠ same condition
THBD p.Arg567Gln Uncertain significance ★★ ⚠ same condition
THBD p.Arg83Gly Uncertain significance ★★ ⚠ same condition
THBD p.Asn115Asp Uncertain significance ★★ ⚠ same condition

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-phe197val (accessed [today's date]).

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