Is TAAR5 p.Arg330Cys (c.988C>T) pathogenic?

TAAR5 p.Arg330Cys (c.988C>T) is classified Benign in TAAR5 (ClinVar, Single submitter, 1 submitter; last evaluated 2019-12-31). AlphaMissense: likely benign (0.1427); Common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele.

What do computational predictors say about TAAR5 p.Arg330Cys (c.988C>T)?

AlphaMissense predicts likely benign (score 0.1427) — an in-silico prediction, not a clinical call.

TAAR5 p.Arg330Cys

Q: How common is TAAR5 p.Arg330Cys (c.988C>T) in the general population?

TAAR5 p.Arg330Cys (c.988C>T) is common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele (gnomAD).

c.988C>T · rs35839363 · VCV783474

Benign Single submitter

Classification

Benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1427 · ACMG-weighted

gnomAD v4.1

Common

common (popmax 10.2%, afr) — too common for a highly-penetrant pathogenic allele

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1427	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -7.83	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 0.19	GERP -2.9
Regional constraint	o/e 1.22	unconstrained · MANE · 1,010 bp · p 9e-06 · regional, not allelic
Overall
CADD	17.52	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 10.2% African / African-American · 7,614/74,904 alleles

Filtering AF 9.97% ClinGen BA1/BS1 input FAF95, joint · FAF99 9.9%

Overall 0.569% 9,185/1,613,532 alleles · common exomes 4,909/1,461,436 · genomes 4,276/152,096 · joint denominator

Ancestry group	Frequency	1 in
African / African-Americangrpmax	10.2%	10
Remaining individualsnot grpmax-eligible	0.743%	135
Admixed American	0.662%	151
Middle Eastern	0.611%	164
European (non-Finnish)	0.0551%	1,815
Ashkenazi Jewishnot grpmax-eligible	0.0372%	2,688
South Asian	0.0121%	8,273
Finnishnot grpmax-eligible	0.00156%	63,994

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: TAAR5
Protein: p.Arg330Cys
Coding: c.988C>T
MANE Select: NM_003967
dbSNP: rs35839363
Type: single nucleotide variant
Location: chr6:132588699 (GRCh38)
Gene constraint: LOEUF 1.685 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 84.94
Residue 330: a UniProt-annotated variant site (in)

Full TAAR5 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

TAAR5 p.Arg330Pro Likely benign ★ same residue
TAAR5 p.Thr272Met Benign/Likely benign ★★ same type
TAAR5 p.Ala230Val Uncertain significance ★ ⚠ same type
TAAR5 p.Ala40Asp Uncertain significance ★ ⚠ same type
TAAR5 p.Ala58Pro Uncertain significance ★ ⚠ same type
TAAR5 p.Arg108Leu Uncertain significance ★ ⚠ same type
TAAR5 p.Arg108Pro Uncertain significance ★ same type
TAAR5 p.Arg26Lys Uncertain significance ★ ⚠ 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/taar5-p-arg330cys (accessed [today's date]).

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