Is CD53 p.Ile217Thr (c.650T>C) pathogenic?

CD53 p.Ile217Thr (c.650T>C) is classified Uncertain significance in CD53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-02). AlphaMissense: likely benign (0.0681); Rare (popmax 0.153%, sas).

How common is CD53 p.Ile217Thr (c.650T>C) in the general population?

CD53 p.Ile217Thr (c.650T>C) is rare (popmax 0.153%, sas) (gnomAD).

What do computational predictors say about CD53 p.Ile217Thr (c.650T>C)?

AlphaMissense predicts likely benign (score 0.0681) — an in-silico prediction, not a clinical call.

CD53 p.Ile217Thr

c.650T>C · VCV4222953

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0681 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.153%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0681	likely benign
REVEL	0.119	moderately benign-leaning
SaProt	LLR -5.81	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 7,783 bp · p 0.0032 · regional, not allelic
Overall
CADD	21.6	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.153% South Asian · 139/91,060 alleles

Filtering AF 0.132% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.124%

Overall 0.0221% 356/1,612,506 alleles · rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.153%	655
European (non-Finnish)	0.0163%	6,138
Finnishnot grpmax-eligible	0.0156%	6,400
Remaining individualsnot grpmax-eligible	0.00961%	10,410
African / African-American	0.00933%	10,716
East Asian	0.00223%	44,870
Admixed American	0.00167%	60,010

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: CD53
Protein: p.Ile217Thr
Coding: c.650T>C
MANE Select: NM_000560
Type: single nucleotide variant
Location: chr1:110899185 (GRCh38)
Gene constraint: LOEUF 0.912 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 93.05 · 1 PDB

Full CD53 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CD53 p.Ala172Val Uncertain significance ★ ⚠ same type
CD53 p.Arg124His Uncertain significance ★ ⚠ same type
CD53 p.Asp120Asn Uncertain significance ★ ⚠ same type
CD53 p.Gly117Asp Uncertain significance ★ ⚠ same type
CD53 p.Gly117Val Uncertain significance ★ ⚠ same type
CD53 p.Gly156Ser Uncertain significance ★ ⚠ same type
CD53 p.His45Arg Uncertain significance ★ ⚠ same type
CD53 p.Ile122Thr 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/cd53-p-ile217thr (accessed [today's date]).

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