Is CYSRT1 p.Arg110His (c.329G>A) pathogenic?

CYSRT1 p.Arg110His (c.329G>A) is classified Uncertain significance in CYSRT1 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-08-04). AlphaMissense: likely benign (0.0912); Ultra-rare (popmax 0.034%, mid).

How common is CYSRT1 p.Arg110His (c.329G>A) in the general population?

CYSRT1 p.Arg110His (c.329G>A) is ultra-rare (popmax 0.034%, mid) (gnomAD).

What do computational predictors say about CYSRT1 p.Arg110His (c.329G>A)?

AlphaMissense predicts likely benign (score 0.0912) — an in-silico prediction, not a clinical call.

CYSRT1 p.Arg110His

c.329G>A · rs890811316 · VCV2603273

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0912 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.034%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0912	likely benign
REVEL	0.032	moderately benign-leaning
SaProt	LLR -6.12	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 0.82	GERP -0.065, phastCons 0.15
Regional constraint	o/e 0.96	unconstrained · MANE · 431 bp · p 0.55 · regional, not allelic
Overall
CADD	19.68	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

Grpmax group 0.034% Middle Eastern · 2/5,890 alleles

Filtering AF 0.00635% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00434%

Overall 0.00284% 44/1,548,072 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.034%	2,945
East Asian	0.0147%	6,819
Ashkenazi Jewishnot grpmax-eligible	0.0035%	28,610
African / African-American	0.00274%	36,519
European (non-Finnish)	0.0027%	36,985
Admixed American	0.00196%	50,948
South Asian	0.00119%	84,006

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: CYSRT1
Protein: p.Arg110His
Coding: c.329G>A
MANE Select: NM_199001
dbSNP: rs890811316
Type: single nucleotide variant
Location: chr9:137225950 (GRCh38)
Gene constraint: LOEUF 1.892 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 56.71

Full CYSRT1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CYSRT1 p.Ala76Ser Uncertain significance ★ ⚠ same type
CYSRT1 p.Ala98Asp Uncertain significance ★ ⚠ same type
CYSRT1 p.Arg134Cys Uncertain significance ★ ⚠ same type
CYSRT1 p.Arg134His Uncertain significance ★ ⚠ same type
CYSRT1 p.Arg96His Uncertain significance ★ ⚠ same type
CYSRT1 p.Asp2Glu Uncertain significance ★ ⚠ same type
CYSRT1 p.Cys118Arg Uncertain significance ★ ⚠ same type
CYSRT1 p.Cys138Tyr 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/cysrt1-p-arg110his (accessed [today's date]).

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