Is ENDOV p.Pro10Gln (c.29C>A) pathogenic?

ENDOV p.Pro10Gln (c.29C>A) is classified Uncertain significance in ENDOV (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-17). AlphaMissense: likely benign (0.0781); Ultra-rare (popmax 0.0133%, afr).

How common is ENDOV p.Pro10Gln (c.29C>A) in the general population?

ENDOV p.Pro10Gln (c.29C>A) is ultra-rare (popmax 0.0133%, afr) (gnomAD).

What do computational predictors say about ENDOV p.Pro10Gln (c.29C>A)?

AlphaMissense predicts likely benign (score 0.0781) — an in-silico prediction, not a clinical call.

ENDOV p.Pro10Gln

c.29C>A · rs375994328 · VCV2251118

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0781 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0133%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0781	likely benign
REVEL	0.006	strongly benign-leaning
SaProt	LLR -8.32	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 -0.005	GERP -2
Regional constraint	o/e 1.17	unconstrained · MANE · 21 kb · p 0.00075 · regional, not allelic
Overall
CADD	11.3	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 0.0133% African / African-American · 10/74,928 alleles

Filtering AF 0.00723% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0055%

Overall 0.000868% 14/1,613,248 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0133%	7,493
European (non-Finnish)	0.000339%	294,932

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.Pro10Gln
Coding: c.29C>A
MANE Select: NM_173627
dbSNP: rs375994328
Type: single nucleotide variant
Location: chr17:80415223 (GRCh38)
Gene constraint: LOEUF 1.439 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.90 · 2 PDB

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

Similar variants

ENDOV p.Pro10Arg Uncertain significance ★ ⚠ same residue
ENDOV p.Pro10Leu Uncertain significance ★ ⚠ same residue
ENDOV p.Pro10Ser 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

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-pro10gln (accessed [today's date]).

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