Is ENDOV p.Ala35Gly (c.104C>G) pathogenic?

ENDOV p.Ala35Gly (c.104C>G) is classified Uncertain significance in ENDOV (ClinVar, Single submitter, 1 submitter; last evaluated 2025-08-05). AlphaMissense: likely benign (0.1116); Very rare (popmax 0.00134%, afr).

How common is ENDOV p.Ala35Gly (c.104C>G) in the general population?

ENDOV p.Ala35Gly (c.104C>G) is very rare (popmax 0.00134%, afr) (gnomAD).

What do computational predictors say about ENDOV p.Ala35Gly (c.104C>G)?

AlphaMissense predicts likely benign (score 0.1116) — an in-silico prediction, not a clinical call.

ENDOV p.Ala35Gly

c.104C>G · VCV4249000

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1116 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00134%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1116	likely benign
REVEL	0.034	moderately benign-leaning
SaProt	LLR -6.78	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.22 · evaluated, not missing
Constraint at this position
Conservation	phyloP 4.5	GERP 1.1, phastCons 1
Regional constraint	o/e 1.17	unconstrained · MANE · 21 kb · p 0.00075 · regional, not allelic
Overall
CADD	20.7	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 0.00134% African / African-American · 1/74,904 alleles

Filtering AF 0.000615% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000474%

Overall 0.000869% 14/1,611,610 alleles · very rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.00134%	74,904
European (non-Finnish)	0.0011%	90,696

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.Ala35Gly
Coding: c.104C>G
MANE Select: NM_173627
Type: single nucleotide variant
Location: chr17:80415697 (GRCh38)
Gene constraint: LOEUF 1.439 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.90 · 2 PDB
Residue 35: an α-helix

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.Ala264Val 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-ala35gly (accessed [today's date]).

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