Is CDS2 p.Val101Ile (c.301G>A) pathogenic?

CDS2 p.Val101Ile (c.301G>A) is classified Uncertain significance in CDS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-11). AlphaMissense: likely benign (0.0878); Ultra-rare (popmax 0.0264%, nfe).

How common is CDS2 p.Val101Ile (c.301G>A) in the general population?

CDS2 p.Val101Ile (c.301G>A) is ultra-rare (popmax 0.0264%, nfe) (gnomAD).

What do computational predictors say about CDS2 p.Val101Ile (c.301G>A)?

AlphaMissense predicts likely benign (score 0.0878) — an in-silico prediction, not a clinical call.

CDS2 p.Val101Ile

c.301G>A · rs370528801 · VCV2207438

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0878 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0264%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0878	likely benign
REVEL	0.197	benign-leaning
SaProt	LLR -6.66	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 12	GERP 0.93, phastCons 1
Regional constraint	o/e 0.82	unconstrained · MANE · 50 kb · p 0.046 · regional, not allelic
Overall
CADD	22.9	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 0.0264% European (non-Finnish) · 311/1,179,158 alleles

Filtering AF 0.0239% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0229%

Overall 0.0205% 330/1,613,038 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0264%	3,791
Remaining individualsnot grpmax-eligible	0.00961%	10,409
African / African-American	0.00668%	14,977
East Asian	0.00446%	22,436
South Asian	0.00439%	22,766
Admixed American	0.00333%	29,995

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: CDS2
Protein: p.Val101Ile
Coding: c.301G>A
MANE Select: NM_003818
dbSNP: rs370528801
Type: single nucleotide variant
Location: chr20:5176657 (GRCh38)
Gene constraint: LOEUF 0.944 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.70

Full CDS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CDS2 p.Ala346Ser Uncertain significance ★ ⚠ same type
CDS2 p.Ala398Thr Uncertain significance ★ ⚠ same type
CDS2 p.Arg167Trp Uncertain significance ★ ⚠ same type
CDS2 p.Arg311His Uncertain significance ★ ⚠ same type
CDS2 p.Arg429Gln Uncertain significance ★ ⚠ same type
CDS2 p.Asn426Ser Uncertain significance ★ ⚠ same type
CDS2 p.Asp147Gly Uncertain significance ★ ⚠ same type
CDS2 p.Gly378Asp 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/cds2-p-val101ile (accessed [today's date]).

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