Is GDNF p.Arg41Ser (c.121C>A) pathogenic?

GDNF p.Arg41Ser (c.121C>A) is classified Uncertain significance in GDNF (ClinVar, Single submitter, 1 submitter; last evaluated 2020-03-04). AlphaMissense: likely benign (0.1969); Absent from gnomAD v4.1.

How common is GDNF p.Arg41Ser (c.121C>A) in the general population?

GDNF p.Arg41Ser (c.121C>A) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GDNF p.Arg41Ser (c.121C>A)?

AlphaMissense predicts likely benign (score 0.1969) — an in-silico prediction, not a clinical call.

GDNF p.Arg41Ser

c.121C>A · rs1750637562 · VCV1320480

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1969 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,605,844)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1969	likely benign
REVEL	0.284	benign-leaning
SaProt	LLR -6.00	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 9.8	GERP 1.9, phastCons 1
Regional constraint	o/e 0.90	unconstrained · MANE · 19 kb · p 0.087 · regional, not allelic
Overall
CADD	22.6	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

No allele count reported in gnomAD v4.1 (AN 1,605,844). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: GDNF
Protein: p.Arg41Ser
Coding: c.121C>A
MANE Select: NM_000514
dbSNP: rs1750637562
Type: single nucleotide variant
Location: chr5:37834676 (GRCh38)
Gene constraint: LOEUF 0.725 · pLI 0.60 (gnomAD)
Structure: AlphaFold pLDDT 75.29 · 4 PDB
Residue 41: the 'disordered' region

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

Similar variants

GDNF c.*2213G>A Uncertain significance ★★ same type
GDNF c.*2828T>A Uncertain significance ★★ same type
GDNF p.Arg116Gln Uncertain significance ★★ ⚠ same type
ATF1 p.Tyr109= Benign ★★ same type
ATF2 p.Asn348= Benign ★★ same type
ATF2 p.Asp440= Benign ★★ same type
GDNF c.152-73C>T Benign ★★ same type
GDNF c.-51A>G 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/gdnf-p-arg41ser (accessed [today's date]).

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