Is ENDOV p.Ala264Val (c.791C>T) pathogenic?

ENDOV p.Ala264Val (c.791C>T) is classified Uncertain significance in ENDOV (ClinVar, Single submitter, 1 submitter; last evaluated 2023-03-02). AlphaMissense: likely benign (0.0774); Very rare (popmax 0.00223%, sas).

How common is ENDOV p.Ala264Val (c.791C>T) in the general population?

ENDOV p.Ala264Val (c.791C>T) is very rare (popmax 0.00223%, sas) (gnomAD).

What do computational predictors say about ENDOV p.Ala264Val (c.791C>T)?

AlphaMissense predicts likely benign (score 0.0774) — an in-silico prediction, not a clinical call.

ENDOV p.Ala264Val

c.791C>T · rs372710137 · VCV2493569

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0774 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0774	likely benign
REVEL	0.048	moderately benign-leaning
SaProt	LLR -7.39	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 -2.4	GERP -2.5
Regional constraint	o/e 1.17	unconstrained · MANE · 21 kb · p 0.00075 · regional, not allelic
Overall
CADD	12.0	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 0.00223% South Asian · 2/89,496 alleles

Filtering AF 0.00122% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00104%

Overall 0.00156% 25/1,603,478 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00223%	44,748
European (non-Finnish)	0.00187%	53,500
African / African-American	0.00135%	74,342

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: ENDOV
Protein: p.Ala264Val
Coding: c.791C>T
MANE Select: NM_173627
dbSNP: rs372710137
Type: single nucleotide variant
Location: chr17:80429784 (GRCh38)
Gene constraint: LOEUF 1.439 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.90 · 2 PDB
Residue 264: the 'disordered' region

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

Similar variants

ENDOV p.His141Tyr Benign ★★ same type
ENDOV p.Ala167Thr Uncertain significance ★ ⚠ same type
ENDOV p.Ala220Val Uncertain significance ★ ⚠ same type
ENDOV p.Ala239Pro Uncertain significance ★ ⚠ same type
ENDOV p.Ala35Gly Uncertain significance ★ ⚠ same type
ENDOV p.Ala41Thr Uncertain significance ★ ⚠ same type
ENDOV p.Ala63Gly Uncertain significance ★ ⚠ same type
ENDOV p.Ala65Ser 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/endov-p-ala264val (accessed [today's date]).

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