Is ENDOD1 p.Tyr347Phe (c.1040A>T) pathogenic?

ENDOD1 p.Tyr347Phe (c.1040A>T) is classified Uncertain significance in ENDOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-08). AlphaMissense: likely benign (0.1202); Ultra-rare (popmax 0.0495%, mid).

How common is ENDOD1 p.Tyr347Phe (c.1040A>T) in the general population?

ENDOD1 p.Tyr347Phe (c.1040A>T) is ultra-rare (popmax 0.0495%, mid) (gnomAD).

What do computational predictors say about ENDOD1 p.Tyr347Phe (c.1040A>T)?

AlphaMissense predicts likely benign (score 0.1202) — an in-silico prediction, not a clinical call.

ENDOD1 p.Tyr347Phe

c.1040A>T · rs551599857 · VCV2327768

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1202 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0495%, mid)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1202	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -5.83	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	GERP -3.7, phastCons 0.87
Regional constraint	o/e 1.02	unconstrained · MANE · 40 kb · p 0.62 · regional, not allelic
Overall
CADD	8.664	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 0.0495% Middle Eastern · 3/6,062 alleles

Filtering AF 0.0331% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0293%

Overall 0.00496% 80/1,614,112 alleles · ultra-rare

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0495%	2,021
South Asian	0.0439%	2,277
Remaining individualsnot grpmax-eligible	0.0128%	7,813
Admixed American	0.00333%	30,013
European (non-Finnish)	0.0022%	45,386
African / African-American	0.00133%	75,018

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.Tyr347Phe
Coding: c.1040A>T
MANE Select: NM_015036
dbSNP: rs551599857
Type: single nucleotide variant
Location: chr11:95129116 (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-tyr347phe (accessed [today's date]).

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