Is ECD p.His298Arg (c.893A>G) pathogenic?

ECD p.His298Arg (c.893A>G) is classified Uncertain significance in ECD (ClinVar, Single submitter, 1 submitter; last evaluated 2021-09-01). AlphaMissense: likely benign (0.1118); Ultra-rare (popmax 0.0792%, nfe).

How common is ECD p.His298Arg (c.893A>G) in the general population?

ECD p.His298Arg (c.893A>G) is ultra-rare (popmax 0.0792%, nfe) (gnomAD).

What do computational predictors say about ECD p.His298Arg (c.893A>G)?

AlphaMissense predicts likely benign (score 0.1118) — an in-silico prediction, not a clinical call.

ECD p.His298Arg

c.893A>G · rs142804992 · VCV3086890

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1118 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0792%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1118	likely benign
REVEL	0.222	benign-leaning
SaProt	LLR -4.10	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 7.8	GERP 2.1, phastCons 1
Overall
CADD	25.0	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 0.0792% European (non-Finnish) · 934/1,179,500 alleles

Filtering AF 0.0749% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0732%

Overall 0.0614% 990/1,613,462 alleles · ultra-rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.0792%	1,263
Remaining individualsnot grpmax-eligible	0.0512%	1,952
Admixed American	0.0183%	5,452
African / African-American	0.0173%	5,772

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: ECD
Protein: p.His298Arg
Coding: c.893A>G
MANE Select: NM_006304 · reported on NM_007265
dbSNP: rs142804992
Type: single nucleotide variant
Location: chr10:73152312 (GRCh38)
Structure: AlphaFold pLDDT 69.87 · 140 PDB

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

Similar variants

ECD p.Ala121Gly Uncertain significance ★ same type
ECD p.Ala122Ser Uncertain significance ★ ⚠ same type
ECD p.Ala150Thr Uncertain significance ★ ⚠ same type
ECD p.Ala234Ser Uncertain significance ★ ⚠ same type
ECD p.Ala329Val Uncertain significance ★ ⚠ same type
ECD p.Arg188Leu Uncertain significance ★ ⚠ same type
ECD p.Arg244Gln Uncertain significance ★ ⚠ same type
ECD p.Arg281Gln 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/ecd-p-his298arg (accessed [today's date]).

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