Is GRM6 p.Ala71Ser (c.211G>T) pathogenic?

GRM6 p.Ala71Ser (c.211G>T) is classified Uncertain significance in GRM6 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-26). AlphaMissense: ambiguous (0.5201); Absent from gnomAD v4.1; Associated with Inborn genetic diseases.

What condition is associated with GRM6 p.Ala71Ser (c.211G>T)?

GRM6 p.Ala71Ser (c.211G>T) is associated with Inborn genetic diseases (ClinVar).

How common is GRM6 p.Ala71Ser (c.211G>T) in the general population?

GRM6 p.Ala71Ser (c.211G>T) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about GRM6 p.Ala71Ser (c.211G>T)?

AlphaMissense predicts ambiguous (score 0.5201) — an in-silico prediction, not a clinical call.

GRM6 p.Ala71Ser

c.211G>T · rs1349624080 · VCV2552349

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5201 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,460,138)

Missense predictors

2/2 damaging

REVEL, SaProt · AlphaMissense no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.5201	ambiguous
REVEL	0.711	pathogenic-leaning
SaProt	LLR -11.76	damaging
⇒ REVEL and SaProt both call this damaging; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 2.1, phastCons 1
Regional constraint	o/e 1.00	unconstrained · MANE · 13 kb · p 0.88 · regional, not allelic
Overall
CADD	26.3	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

No allele count reported in gnomAD v4.1 (AN 1,460,138). 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: GRM6
Protein: p.Ala71Ser
Coding: c.211G>T
MANE Select: NM_000843
dbSNP: rs1349624080
Type: single nucleotide variant
Location: chr5:178994734 (GRCh38)
Gene constraint: LOEUF 1.229 · pLI <0.01 · ClinGen HI gene assoc. with recessive phenotype (gnomAD)
Structure: AlphaFold pLDDT 85.90 · 5 PDB
Residue 71: a disulfide bond

Full GRM6 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRM6 p.Ala71Thr Uncertain significance ★ ⚠ same residue
GRM6 p.Ala240Pro Uncertain significance ★★ ⚠ same condition
GRM6 p.Ala414Thr Uncertain significance ★★ ⚠ same condition
GRM6 p.Ala421Val Uncertain significance ★★ ⚠ same condition
GRM6 p.Ala432Val Uncertain significance ★★ ⚠ same condition
GRM6 p.Ala466Val Uncertain significance ★★ ⚠ same condition
GRM6 p.Ala482Thr Uncertain significance ★★ ⚠ same condition
GRM6 p.Ala586Thr Uncertain significance ★★ ⚠ same condition

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/grm6-p-ala71ser (accessed [today's date]).

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