Is ENDOD1 p.Lys341Arg (c.1022A>G) pathogenic?

ENDOD1 p.Lys341Arg (c.1022A>G) is classified Uncertain significance in ENDOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-26). AlphaMissense: likely benign (0.0932); Very rare (popmax 0.00237%, nfe).

How common is ENDOD1 p.Lys341Arg (c.1022A>G) in the general population?

ENDOD1 p.Lys341Arg (c.1022A>G) is very rare (popmax 0.00237%, nfe) (gnomAD).

What do computational predictors say about ENDOD1 p.Lys341Arg (c.1022A>G)?

AlphaMissense predicts likely benign (score 0.0932) — an in-silico prediction, not a clinical call.

ENDOD1 p.Lys341Arg

c.1022A>G · VCV4248974

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0932 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00237%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0932	likely benign
REVEL	0.024	moderately benign-leaning
SaProt	LLR -7.55	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 1.4	GERP -2, phastCons 0.29
Regional constraint	o/e 1.02	unconstrained · MANE · 40 kb · p 0.62 · regional, not allelic
Overall
CADD	15.29	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 0.00237% European (non-Finnish) · 28/1,180,032 alleles

Filtering AF 0.00164% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00142%

Overall 0.00173% 28/1,614,018 alleles · very rare

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: ENDOD1
Protein: p.Lys341Arg
Coding: c.1022A>G
MANE Select: NM_015036
Type: single nucleotide variant
Location: chr11:95129098 (GRCh38)
Gene constraint: LOEUF 1.843 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 81.44

Full ENDOD1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ENDOD1 p.Ala320Val Uncertain significance ★ ⚠ same type
ENDOD1 p.Ala352Glu Uncertain significance ★ ⚠ same type
ENDOD1 p.Ala438Thr Uncertain significance ★ ⚠ same type
ENDOD1 p.Ala45Ser Uncertain significance ★ ⚠ same type
ENDOD1 p.Ala80Thr Uncertain significance ★ ⚠ same type
ENDOD1 p.Ala83Ser Uncertain significance ★ ⚠ same type
ENDOD1 p.Arg173Trp Uncertain significance ★ ⚠ same type
ENDOD1 p.Arg241Trp 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/endod1-p-lys341arg (accessed [today's date]).

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