Is ENDOD1 p.Phe260Cys (c.779T>G) pathogenic?

ENDOD1 p.Phe260Cys (c.779T>G) is classified Uncertain significance in ENDOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-27). AlphaMissense: likely benign (0.1706); Ultra-rare (popmax 0.0425%, nfe).

How common is ENDOD1 p.Phe260Cys (c.779T>G) in the general population?

ENDOD1 p.Phe260Cys (c.779T>G) is ultra-rare (popmax 0.0425%, nfe) (gnomAD).

What do computational predictors say about ENDOD1 p.Phe260Cys (c.779T>G)?

AlphaMissense predicts likely benign (score 0.1706) — an in-silico prediction, not a clinical call.

ENDOD1 p.Phe260Cys

c.779T>G · VCV3508454

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1706 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0425%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1706	likely benign
REVEL	0.084	moderately benign-leaning
SaProt	LLR -5.53	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 -0.5	GERP -3.7
Regional constraint	o/e 1.02	unconstrained · MANE · 40 kb · p 0.62 · regional, not allelic
Overall
CADD	15.04	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 0.0425% European (non-Finnish) · 502/1,180,022 alleles

Filtering AF 0.0394% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0382%

Overall 0.033% 533/1,614,150 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0425%	2,351
Admixed American	0.0233%	4,288
Remaining individualsnot grpmax-eligible	0.0176%	5,683
African / African-American	0.008%	12,504

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.Phe260Cys
Coding: c.779T>G
MANE Select: NM_015036
Type: single nucleotide variant
Location: chr11:95128855 (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-phe260cys (accessed [today's date]).

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