Is THBD p.Val111Phe (c.331G>T) pathogenic?

THBD p.Val111Phe (c.331G>T) is classified Uncertain significance in THBD (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-01-17). AlphaMissense: ambiguous (0.5427); No allele count reported in gnomAD v4.1 (AN 1,578,236); Associated with Inborn genetic diseases.

What condition is associated with THBD p.Val111Phe (c.331G>T)?

THBD p.Val111Phe (c.331G>T) is associated with Inborn genetic diseases (ClinVar).

How common is THBD p.Val111Phe (c.331G>T) in the general population?

THBD p.Val111Phe (c.331G>T) is no allele count reported in gnomAD v4.1 (AN 1,578,236) (gnomAD).

What do computational predictors say about THBD p.Val111Phe (c.331G>T)?

AlphaMissense predicts ambiguous (score 0.5427) — an in-silico prediction, not a clinical call.

THBD p.Val111Phe

c.331G>T · rs886056549 · VCV2623738

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.5427 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,578,236)

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5427	ambiguous
REVEL	0.34	indeterminate
SaProt	LLR -12.49	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.5	GERP 1.7, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,724 bp · p 0.25 · regional, not allelic
Overall
CADD	28.6	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 1,578,236). 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.Val111Phe
Coding: c.331G>T
MANE Select: NM_000361
dbSNP: rs886056549
Type: single nucleotide variant
Location: chr20:23049174 (GRCh38)
Gene constraint: LOEUF 1.938 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 79.35 · 13 PDB
Residue 111: the c-type lectin domain

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.Val111Ile Uncertain significance ★ ⚠ 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-val111phe (accessed [today's date]).

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