Is DERL1 p.Ile34Val (c.100A>G) pathogenic?

DERL1 p.Ile34Val (c.100A>G) is classified Uncertain significance in DERL1 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-10-29). AlphaMissense: likely benign (0.0824); Very rare (popmax 0.00833%, amr).

How common is DERL1 p.Ile34Val (c.100A>G) in the general population?

DERL1 p.Ile34Val (c.100A>G) is very rare (popmax 0.00833%, amr) (gnomAD).

What do computational predictors say about DERL1 p.Ile34Val (c.100A>G)?

AlphaMissense predicts likely benign (score 0.0824) — an in-silico prediction, not a clinical call.

DERL1 p.Ile34Val

c.100A>G · rs765222212 · VCV2409460

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0824 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00833%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0824	likely benign
REVEL	0.076	moderately benign-leaning
SaProt	LLR -6.51	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 2.9	GERP 1.9, phastCons 1
Regional constraint	o/e 0.83	unconstrained · MANE · 27 kb · p 0.0022 · regional, not allelic
Overall
CADD	18.12	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 0.00833% Admixed American · 5/60,010 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.000547% 8/1,461,586 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00833%	12,002
European (non-Finnish)	0.000254%	393,301

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: DERL1
Protein: p.Ile34Val
Coding: c.100A>G
MANE Select: NM_024295
dbSNP: rs765222212
Type: single nucleotide variant
Location: chr8:123042023 (GRCh38)
Gene constraint: LOEUF 0.737 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.76 · 6 PDB

Full DERL1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

DERL1 p.Ile34Asn Uncertain significance ★ ⚠ same residue
DERL1 p.Ala37Pro Uncertain significance ★ ⚠ same type
DERL1 p.Ala45Val Uncertain significance ★ ⚠ same type
DERL1 p.Ala96Val Uncertain significance ★ ⚠ same type
DERL1 p.Arg208His Uncertain significance ★ ⚠ same type
DERL1 p.Asp193His Uncertain significance ★ ⚠ same type
DERL1 p.Asp250Asn Uncertain significance ★ ⚠ same type
DERL1 p.Gln204Arg 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/derl1-p-ile34val (accessed [today's date]).

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