Is ENDOG p.Gly17Ser (c.49G>A) pathogenic?

ENDOG p.Gly17Ser (c.49G>A) is classified Uncertain significance in ENDOG (ClinVar, Single submitter, 1 submitter; last evaluated 2024-07-16). AlphaMissense: ambiguous (0.4426); Very rare (popmax 0.00189%, nfe).

How common is ENDOG p.Gly17Ser (c.49G>A) in the general population?

ENDOG p.Gly17Ser (c.49G>A) is very rare (popmax 0.00189%, nfe) (gnomAD).

What do computational predictors say about ENDOG p.Gly17Ser (c.49G>A)?

AlphaMissense predicts ambiguous (score 0.4426) — an in-silico prediction, not a clinical call.

ENDOG p.Gly17Ser

c.49G>A · VCV3508464

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4426 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00189%, nfe)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense no call

Computational evidence

Protein change
AlphaMissense	0.4426	ambiguous
REVEL	0.274	benign-leaning
SaProt	LLR -11.14	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 9	GERP -0.27, phastCons 1
Regional constraint	o/e 0.93	unconstrained · MANE · 3,922 bp · p 0.17 · regional, not allelic
Overall
CADD	23.7	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 0.00189% European (non-Finnish) · 18/953,182 alleles

Filtering AF 0.00118% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000974%

Overall 0.0017% 20/1,176,680 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00654%	15,298
Remaining individualsnot grpmax-eligible	0.0024%	41,626
European (non-Finnish)grpmax	0.00189%	52,955

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ENDOG
Protein: p.Gly17Ser
Coding: c.49G>A
MANE Select: NM_004435
Type: single nucleotide variant
Location: chr9:128818733 (GRCh38)
Gene constraint: LOEUF 1.847 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 85.67 · 2 PDB

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

Similar variants

ENDOG p.Gly17Val Uncertain significance ★ ⚠ same residue
ENDOG p.Arg184Cys Uncertain significance ★★ ⚠ same type
ENDOG p.Ile218= Benign ★★ same type
ENDOG p.Thr246Ile Benign ★★ ⚠ same type
ENDOG p.Ala130Val Uncertain significance ★ ⚠ same type
ENDOG p.Ala143Asp Uncertain significance ★ ⚠ same type
ENDOG p.Ala14Val Uncertain significance ★ ⚠ same type
ENDOG p.Ala252Val 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/endog-p-gly17ser (accessed [today's date]).

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