Is ALYREF p.Ser201= (c.603C>T) pathogenic?

ALYREF p.Ser201= (c.603C>T) is classified Likely benign in ALYREF (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-21). Ultra-rare (popmax 0.042%, sas).

How common is ALYREF p.Ser201= (c.603C>T) in the general population?

ALYREF p.Ser201= (c.603C>T) is ultra-rare (popmax 0.042%, sas) (gnomAD).

ALYREF p.Ser201=

c.603C>T · VCV3860144

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.042%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.29 · evaluated, not missing
Constraint at this position
Conservation	phyloP -1.6	GERP -3.6
Overall
CADD	1.009	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.042% South Asian · 38/90,396 alleles

Filtering AF 0.0315% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0278%

Overall 0.00394% 63/1,598,472 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.042%	2,379
Admixed American	0.0102%	9,851
Remaining individualsnot grpmax-eligible	0.00808%	12,374
African / African-American	0.00134%	74,720
European (non-Finnish)	0.00111%	90,078

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: ALYREF
Protein: p.Ser201=
Coding: c.603C>T
MANE Select: NM_005782
Type: single nucleotide variant
Location: chr17:81888418 (GRCh38)
Gene constraint: LOEUF 0.235 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 65.65 · 4 PDB
Residue 201: the 'disordered' region; the 'rna-binding domain 2' region

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

Similar variants

ALYREF p.Gln253Glu Uncertain significance ★ same type
ALYREF p.Pro2His Uncertain significance ★ same type
ALYREF p.Ser4Phe Uncertain significance ★ same type
ALYREF p.Arg231Leu Uncertain significance same type
ALYREF p.Leu16= Likely benign 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/alyref-p-ser201 (accessed [today's date]).

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