Is EOGT p.Arg377Trp (c.1129C>T) pathogenic?

EOGT p.Arg377Trp (c.1129C>T) is classified Uncertain significance in EOGT (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-08-20). AlphaMissense: likely pathogenic (0.9668); Ultra-rare (popmax 0.0241%, afr); Associated with Inborn genetic diseases.

What condition is associated with EOGT p.Arg377Trp (c.1129C>T)?

EOGT p.Arg377Trp (c.1129C>T) is associated with Inborn genetic diseases, Adams-Oliver syndrome 4 (ClinVar).

How common is EOGT p.Arg377Trp (c.1129C>T) in the general population?

EOGT p.Arg377Trp (c.1129C>T) is ultra-rare (popmax 0.0241%, afr) (gnomAD).

What do computational predictors say about EOGT p.Arg377Trp (c.1129C>T)?

AlphaMissense predicts likely pathogenic (score 0.9668) — an in-silico prediction, not a clinical call.

EOGT p.Arg377Trp

c.1129C>T · rs377612780 · VCV1377716

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely pathogenic

0.9668 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0241%, afr)

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Conditions

Inborn genetic diseases

Computational evidence

Protein change
AlphaMissense	0.9668	likely pathogenic · top 10% in EOGT
REVEL	0.533	indeterminate
SaProt	LLR -15.53	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6.5	GERP 1.4, phastCons 1
Regional constraint	o/e 1.10	unconstrained · MANE · 32 kb · p 0.016 · regional, not allelic
Overall
CADD	32.0	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — 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 0.0241% African / African-American · 18/74,818 alleles

Filtering AF 0.0155% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0128%

Overall 0.00291% 47/1,613,276 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0241%	4,157
Admixed American	0.00668%	14,976
European (non-Finnish)	0.00203%	49,158
Remaining individualsnot grpmax-eligible	0.0016%	62,460

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.Arg377Trp
Coding: c.1129C>T
MANE Select: NM_001278689
dbSNP: rs377612780
Type: single nucleotide variant
Location: chr3:68987468 (GRCh38)
Gene constraint: LOEUF 1.121 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 91.71
Residue 377: a UniProt-annotated variant site (in aos4)

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

Disease context

Inborn genetic diseases — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: Adams-Oliver syndrome 4

Similar variants

EOGT p.Arg377Gln Pathogenic 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.Arg149His Uncertain significance ★★ ⚠ same condition
EOGT p.Arg372Trp 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-arg377trp (accessed [today's date]).

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