Is THBD p.Glu155Asp (c.465G>T) pathogenic?

THBD p.Glu155Asp (c.465G>T) is classified Uncertain significance in THBD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2024-03-02). AlphaMissense: likely pathogenic (0.6805); Very rare (popmax 0.00269%, afr).

How common is THBD p.Glu155Asp (c.465G>T) in the general population?

THBD p.Glu155Asp (c.465G>T) is very rare (popmax 0.00269%, afr) (gnomAD).

What do computational predictors say about THBD p.Glu155Asp (c.465G>T)?

AlphaMissense predicts likely pathogenic (score 0.6805) — an in-silico prediction, not a clinical call.

THBD p.Glu155Asp

c.465G>T · rs1159087775 · VCV2662212

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.6805 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00269%, afr)

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.6805	likely pathogenic
REVEL	0.031	moderately benign-leaning
SaProt	LLR -7.31	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.17	GERP 0.66, phastCons 0.95
Regional constraint	o/e 1.04	unconstrained · MANE · 1,724 bp · p 0.25 · regional, not allelic
Overall
CADD	18.19	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

Grpmax group 0.00269% African / African-American · 2/74,342 alleles

Filtering AF 0.000446% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000167%

Overall 0.000127% 2/1,577,248 alleles · very rare exomes 0/1,425,038 · genomes 2/152,210 · 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: THBD
Protein: p.Glu155Asp
Coding: c.465G>T
MANE Select: NM_000361
dbSNP: rs1159087775
Type: single nucleotide variant
Location: chr20:23049040 (GRCh38)
Gene constraint: LOEUF 1.938 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 79.35 · 13 PDB
Residue 155: the c-type lectin domain; a β-strand

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

Similar variants

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
THBD p.Ala272Val Uncertain significance ★★ ⚠ same type
THBD p.Ala284Gly Uncertain significance ★★ ⚠ same type
THBD p.Ala395Val 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-glu155asp (accessed [today's date]).

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