Is DESI2 p.Arg190Cys (c.568C>T) pathogenic?

DESI2 p.Arg190Cys (c.568C>T) is classified Uncertain significance in DESI2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-05-31). AlphaMissense: likely benign (0.1379); Ultra-rare (popmax 0.0176%, sas).

How common is DESI2 p.Arg190Cys (c.568C>T) in the general population?

DESI2 p.Arg190Cys (c.568C>T) is ultra-rare (popmax 0.0176%, sas) (gnomAD).

What do computational predictors say about DESI2 p.Arg190Cys (c.568C>T)?

AlphaMissense predicts likely benign (score 0.1379) — an in-silico prediction, not a clinical call.

DESI2 p.Arg190Cys

c.568C>T · rs141603902 · VCV2562715

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1379 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0176%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1379	likely benign
REVEL	0.141	moderately benign-leaning
SaProt	LLR -8.85	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 7.6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 154 bp · p 0.15 · regional, not allelic
Overall
CADD	25.5	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 0.0176% South Asian · 16/91,058 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00889%

Overall 0.00491% 79/1,609,946 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0176%	5,691
Middle Eastern	0.0166%	6,016
Remaining individualsnot grpmax-eligible	0.00961%	10,406
East Asian	0.00669%	14,957
European (non-Finnish)	0.00424%	23,585
African / African-American	0.004%	24,999

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: DESI2
Protein: p.Arg190Cys
Coding: c.568C>T
MANE Select: NM_016076
dbSNP: rs141603902
Type: single nucleotide variant
Location: chr1:244705772 (GRCh38)
Gene constraint: LOEUF 0.811 · pLI 0.59 (gnomAD)
Structure: AlphaFold pLDDT 86.26
Residue 190: the 'disordered' region

Full DESI2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DESI2 p.Ala153Ser Uncertain significance ★ ⚠ same type
DESI2 p.Ala153Thr Uncertain significance ★ ⚠ same type
DESI2 p.Ala175Thr Uncertain significance ★ ⚠ same type
DESI2 p.Arg126Cys Uncertain significance ★ ⚠ same type
DESI2 p.Arg126His Uncertain significance ★ ⚠ same type
DESI2 p.Asp172Asn Uncertain significance ★ ⚠ same type
DESI2 p.Glu123Asp Uncertain significance ★ ⚠ same type
DESI2 p.Gly185Val 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/desi2-p-arg190cys (accessed [today's date]).

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