Is CD53 p.Val57Phe (c.169G>T) pathogenic?

CD53 p.Val57Phe (c.169G>T) is classified Uncertain significance in CD53 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-10-29). AlphaMissense: ambiguous (0.3708); Very rare (popmax 0.00769%, sas).

How common is CD53 p.Val57Phe (c.169G>T) in the general population?

CD53 p.Val57Phe (c.169G>T) is very rare (popmax 0.00769%, sas) (gnomAD).

What do computational predictors say about CD53 p.Val57Phe (c.169G>T)?

AlphaMissense predicts ambiguous (score 0.3708) — an in-silico prediction, not a clinical call.

CD53 p.Val57Phe

c.169G>T · VCV4650662

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.3708 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00769%, sas)

Computational evidence

Protein change
AlphaMissense	0.3708	ambiguous
REVEL	0.503	indeterminate
SaProt	LLR -12.19	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.62	GERP -4.7
Regional constraint	o/e 0.82	unconstrained · MANE · 7,783 bp · p 0.0032 · regional, not allelic
Overall
CADD	5.018	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 0.00769% South Asian · 7/91,076 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.00198% 32/1,613,974 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00769%	13,011
African / African-American	0.00267%	37,450
European (non-Finnish)	0.00186%	53,636
Remaining individualsnot grpmax-eligible	0.0016%	62,480

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.Val57Phe
Coding: c.169G>T
MANE Select: NM_000560
Type: single nucleotide variant
Location: chr1:110892450 (GRCh38)
Gene constraint: LOEUF 0.912 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 93.05 · 1 PDB
Residue 57: an α-helix

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-val57phe (accessed [today's date]).

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