Is ENDOV p.Leu70Phe (c.208C>T) pathogenic?

ENDOV p.Leu70Phe (c.208C>T) is classified Uncertain significance in ENDOV (ClinVar, Single submitter, 1 submitter; last evaluated 2023-02-17). AlphaMissense: ambiguous (0.5433); Very rare (popmax 0.0052%, amr).

How common is ENDOV p.Leu70Phe (c.208C>T) in the general population?

ENDOV p.Leu70Phe (c.208C>T) is very rare (popmax 0.0052%, amr) (gnomAD).

What do computational predictors say about ENDOV p.Leu70Phe (c.208C>T)?

AlphaMissense predicts ambiguous (score 0.5433) — an in-silico prediction, not a clinical call.

ENDOV p.Leu70Phe

c.208C>T · rs767179610 · VCV2469906

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5433 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0052%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.5433	ambiguous
REVEL	0.283	benign-leaning
SaProt	LLR -14.52	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.3	GERP 1.1, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 21 kb · p 0.00075 · regional, not allelic
Overall
CADD	29.3	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 0.0052% Admixed American · 3/57,714 alleles

Filtering AF 0.00138% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000682%

Overall 0.000313% 5/1,598,342 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.0052%	19,238
South Asian	0.00113%	88,494
European (non-Finnish)	8.53e-05%	1,172,670

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.Leu70Phe
Coding: c.208C>T
MANE Select: NM_173627
dbSNP: rs767179610
Type: single nucleotide variant
Location: chr17:80415801 (GRCh38)
Gene constraint: LOEUF 1.439 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.90 · 2 PDB
Residue 70: a β-strand

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

Similar variants

ENDOV p.Leu70Pro Uncertain significance ★ ⚠ same residue
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.Ala264Val Uncertain significance ★ ⚠ same type
ENDOV p.Ala35Gly Uncertain significance ★ ⚠ same type
ENDOV p.Ala41Thr 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-leu70phe (accessed [today's date]).

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