Is GRM5 p.Ala995Val (c.2984C>T) pathogenic?

GRM5 p.Ala995Val (c.2984C>T) is classified Likely benign in GRM5 (ClinVar, Single submitter, 1 submitter; last evaluated 2026-02-07). AlphaMissense: likely benign (0.0881); Very rare (popmax 0.00255%, sas); Associated with autism spectrum disorder.

What condition is associated with GRM5 p.Ala995Val (c.2984C>T)?

GRM5 p.Ala995Val (c.2984C>T) is associated with autism spectrum disorder (ClinVar).

How common is GRM5 p.Ala995Val (c.2984C>T) in the general population?

GRM5 p.Ala995Val (c.2984C>T) is very rare (popmax 0.00255%, sas) (gnomAD).

What do computational predictors say about GRM5 p.Ala995Val (c.2984C>T)?

AlphaMissense predicts likely benign (score 0.0881) — an in-silico prediction, not a clinical call.

GRM5 p.Ala995Val

c.2984C>T · VCV4851336

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0881 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00255%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Conditions

autism spectrum disorder

Computational evidence

Protein change
AlphaMissense	0.0881	likely benign
REVEL	0.263	benign-leaning
SaProt	LLR -7.73	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 5.8	GERP -0.96, phastCons 0.99
Regional constraint	o/e 1.06	unconstrained · MANE · 59 kb · p 0.2 · regional, not allelic
Overall
CADD	13.88	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 0.00255% South Asian · 2/78,428 alleles

Filtering AF 0.000423% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000158%

Overall 0.000299% 4/1,339,910 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00255%	39,214
European (non-Finnish)	0.000178%	562,054

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: GRM5
Protein: p.Ala995Val
Coding: c.2984C>T
MANE Select: NM_001143831
Type: single nucleotide variant
Location: chr11:88509247 (GRCh38)
Gene constraint: LOEUF 0.43 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 72.16 · 30 PDB

Full GRM5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

autism spectrum disorder — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

GRM5 c.1691-4G>T Likely benign ★★ same type
GRM5 p.Arg925= Likely benign ★★ same type
GRM5 p.Asn402= Benign ★★ same type
GRM5 p.Gln63= Benign ★★ same type
GRM5 p.Gly926= Benign ★★ same type
GRM5 p.Gly978Ser Benign ★★ same type
GRM5 p.Lys396= Benign ★★ same type
GRM5 p.Lys678= Benign/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/grm5-p-ala995val (accessed [today's date]).

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