Is GRN p.Ser203= (c.609C>T) pathogenic?

GRN p.Ser203= (c.609C>T) is classified Likely benign in GRN (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-16). Very rare (popmax 0.00329%, sas).

How common is GRN p.Ser203= (c.609C>T) in the general population?

GRN p.Ser203= (c.609C>T) is very rare (popmax 0.00329%, sas) (gnomAD).

GRN p.Ser203=

c.609C>T · VCV4935457

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00329%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.83	GERP 0.015
Overall
CADD	7.221	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00329% South Asian · 3/91,086 alleles

Filtering AF 0.000875% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000443%

Overall 0.000372% 6/1,613,900 alleles · very rare exomes 6/1,461,594 · genomes 0/152,306 · joint denominator

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00329%	30,362
European (non-Finnish)	0.000254%	393,269

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: GRN
Protein: p.Ser203=
Coding: c.609C>T
MANE Select: NM_002087
Type: single nucleotide variant
Location: chr17:44350701 (GRCh38)
Gene constraint: LOEUF 0.59 · pLI 0.04 (gnomAD)
Structure: AlphaFold pLDDT 76.74 · 8 PDB

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

Similar variants

GRN p.Ser203Cys Uncertain significance ★ ⚠ same residue
GRN c.1414-1G>T Pathogenic ★★ same type
GRN c.1414-2A>G Pathogenic ★★ same type
GRN c.264+1G>A Likely pathogenic ★★ same type
GRN c.349+1G>C Pathogenic ★★ same type
GRN c.599-1G>A Pathogenic/Likely pathogenic ★★ same type
GRN c.709-1G>A Pathogenic ★★ same type
GRN c.709-2A>G Pathogenic ★★ 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/grn-p-ser203 (accessed [today's date]).

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