Is CTRL p.Ala73Thr (c.217G>A) pathogenic?

CTRL p.Ala73Thr (c.217G>A) is classified Likely benign in CTRL (ClinVar, No assertion criteria, 1 submitter). AlphaMissense: likely pathogenic (0.8536); Ultra-rare (popmax 0.0178%, eas); Associated with long QT syndrome.

What condition is associated with CTRL p.Ala73Thr (c.217G>A)?

CTRL p.Ala73Thr (c.217G>A) is associated with long QT syndrome (ClinVar).

How common is CTRL p.Ala73Thr (c.217G>A) in the general population?

CTRL p.Ala73Thr (c.217G>A) is ultra-rare (popmax 0.0178%, eas) (gnomAD).

What do computational predictors say about CTRL p.Ala73Thr (c.217G>A)?

AlphaMissense predicts likely pathogenic (score 0.8536) — an in-silico prediction, not a clinical call.

CTRL p.Ala73Thr

c.217G>A · rs752607432 · VCV207886

Likely benign No assertion criteria

Classification

Likely benign

ClinVar

Review

No assertion criteria ☆☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.8536 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, eas)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

long QT syndrome

Computational evidence

Protein change
AlphaMissense	0.8536	likely pathogenic
REVEL	0.607	indeterminate
SaProt	LLR -13.02	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	phastCons 1
Regional constraint	o/e 0.95	unconstrained · MANE · 1,915 bp · p 0.39 · regional, not allelic
Overall
CADD	27.3	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 0.0178% East Asian · 8/44,888 alleles

Filtering AF 0.00883% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00641%

Overall 0.000744% 12/1,613,610 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0178%	5,611
Remaining individualsnot grpmax-eligible	0.0032%	31,244
European (non-Finnish)	0.000169%	590,002

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: CTRL
Protein: p.Ala73Thr
Coding: c.217G>A
MANE Select: NM_001907
dbSNP: rs752607432
Type: single nucleotide variant
Location: chr16:67930939 (GRCh38)
Gene constraint: LOEUF 1.372 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.26
Residue 73: the peptidase s1 domain; a disulfide bond

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

Disease context

long QT syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

CTRL p.Gly230Ser Uncertain significance ★★ ⚠ same type
CTRL p.Glu151Gln Benign ★★ same type
CTRL p.Val70= Benign ★★ same type
CTRL p.Ala131Thr Uncertain significance ★ ⚠ same type
CTRL p.Ala27Thr Uncertain significance ★ ⚠ same type
CTRL p.Arg136His Uncertain significance ★ ⚠ same type
CTRL p.Arg162His Uncertain significance ★ ⚠ same type
CTRL p.Arg188Trp 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/ctrl-p-ala73thr (accessed [today's date]).

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