Is THBD p.Ile71Phe (c.211A>T) pathogenic?

THBD p.Ile71Phe (c.211A>T) is classified Uncertain significance in THBD (ClinVar, Single submitter, 1 submitter; last evaluated 2025-07-15). AlphaMissense: likely pathogenic (0.6681); Very rare (popmax 0.00191%, nfe); Associated with Inborn genetic diseases.

What condition is associated with THBD p.Ile71Phe (c.211A>T)?

THBD p.Ile71Phe (c.211A>T) is associated with Inborn genetic diseases (ClinVar).

How common is THBD p.Ile71Phe (c.211A>T) in the general population?

THBD p.Ile71Phe (c.211A>T) is very rare (popmax 0.00191%, nfe) (gnomAD).

What do computational predictors say about THBD p.Ile71Phe (c.211A>T)?

AlphaMissense predicts likely pathogenic (score 0.6681) — an in-silico prediction, not a clinical call.

THBD p.Ile71Phe

c.211A>T · VCV4183932

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.6681 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00191%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL indeterminate

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.6681	likely pathogenic
REVEL	0.346	indeterminate
SaProt	LLR -6.61	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 6.1	GERP 1.6, phastCons 1
Regional constraint	o/e 1.04	unconstrained · MANE · 1,724 bp · p 0.25 · regional, not allelic
Overall
CADD	24.9	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 0.00191% European (non-Finnish) · 18/943,114 alleles

Filtering AF 0.00119% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000984%

Overall 0.00143% 18/1,263,088 alleles · very rare exomes 17/1,120,896 · genomes 1/142,192 · 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.Ile71Phe
Coding: c.211A>T
MANE Select: NM_000361
Type: single nucleotide variant
Location: chr20:23049294 (GRCh38)
Gene constraint: LOEUF 1.938 · pLI 0.05 (gnomAD)
Structure: AlphaFold pLDDT 79.35 · 13 PDB
Residue 71: the c-type lectin domain; an α-helix

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.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
THBD p.Asn128Ser 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-ile71phe (accessed [today's date]).

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