Is EOGT p.Pro68Ala (c.202C>G) pathogenic?

EOGT p.Pro68Ala (c.202C>G) is classified Uncertain significance in EOGT (ClinVar, Single submitter, 1 submitter; last evaluated 2022-08-10). AlphaMissense: likely benign (0.1477); Very rare (popmax 0.0017%, nfe); Associated with Adams-Oliver syndrome 4.

What condition is associated with EOGT p.Pro68Ala (c.202C>G)?

EOGT p.Pro68Ala (c.202C>G) is associated with Adams-Oliver syndrome 4 (ClinVar).

How common is EOGT p.Pro68Ala (c.202C>G) in the general population?

EOGT p.Pro68Ala (c.202C>G) is very rare (popmax 0.0017%, nfe) (gnomAD).

What do computational predictors say about EOGT p.Pro68Ala (c.202C>G)?

AlphaMissense predicts likely benign (score 0.1477) — an in-silico prediction, not a clinical call.

EOGT p.Pro68Ala

c.202C>G · rs146952006 · VCV2171565

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1477 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0017%, nfe)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Adams-Oliver syndrome 4

Computational evidence

Protein change
AlphaMissense	0.1477	likely benign
REVEL	0.56	indeterminate
SaProt	LLR -12.09	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 12	GERP 2.1, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 32 kb · p 0.016 · regional, not allelic
Overall
CADD	23.0	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 0.0017% European (non-Finnish) · 20/1,178,024 alleles

Filtering AF 0.00111% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000901%

Overall 0.00144% 21/1,459,596 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.00338%	29,588
European (non-Finnish)grpmax	0.0017%	58,901

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: EOGT
Protein: p.Pro68Ala
Coding: c.202C>G
MANE Select: NM_001278689
dbSNP: rs146952006
Type: single nucleotide variant
Location: chr3:69009645 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.71

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

Disease context

Adams-Oliver syndrome 4 — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Similar variants

EOGT p.Pro68= Likely benign ★ same residue
EOGT c.1335-1G>A Pathogenic/Likely pathogenic ★★ same condition
EOGT c.311+1G>T Pathogenic/Likely pathogenic ★★ same condition
EOGT c.621-2A>T Pathogenic/Likely pathogenic ★★ same condition
EOGT p.Arg372Trp Uncertain significance ★★ ⚠ same condition
EOGT p.Arg377Trp Uncertain significance ★★ ⚠ same condition
EOGT p.Arg452His Uncertain significance ★★ ⚠ same condition
EOGT p.Arg470Trp Uncertain significance ★★ ⚠ same condition

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/eogt-p-pro68ala (accessed [today's date]).

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