Is ENDOD1 p.Ala111Val (c.332C>T) pathogenic?

ENDOD1 p.Ala111Val (c.332C>T) is classified Likely benign in ENDOD1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-02-08). AlphaMissense: likely benign (0.0597); Very rare (popmax 0.00432%, nfe).

How common is ENDOD1 p.Ala111Val (c.332C>T) in the general population?

ENDOD1 p.Ala111Val (c.332C>T) is very rare (popmax 0.00432%, nfe) (gnomAD).

What do computational predictors say about ENDOD1 p.Ala111Val (c.332C>T)?

AlphaMissense predicts likely benign (score 0.0597) — an in-silico prediction, not a clinical call.

ENDOD1 p.Ala111Val

c.332C>T · VCV3844815

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0597 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00432%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0597	likely benign
REVEL	0.055	moderately benign-leaning
SaProt	LLR -4.98	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 -1.3	GERP -3.4
Regional constraint	o/e 1.02	unconstrained · MANE · 40 kb · p 0.62 · regional, not allelic
Overall
CADD	0.128	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00432% European (non-Finnish) · 51/1,179,816 alleles

Filtering AF 0.00334% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00302%

Overall 0.00328% 53/1,613,650 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00432%	23,134
African / African-American	0.00133%	74,914
South Asian	0.0011%	91,008

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.Ala111Val
Coding: c.332C>T
MANE Select: NM_015036
Type: single nucleotide variant
Location: chr11:95128408 (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-ala111val (accessed [today's date]).

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