Is ERVV-2 p.His48Arg (c.143A>G) pathogenic?

ERVV-2 p.His48Arg (c.143A>G) is classified Uncertain significance in ERVV-2 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-01-23). AlphaMissense: likely pathogenic (0.5784); Very rare (popmax 0.00549%, eas).

How common is ERVV-2 p.His48Arg (c.143A>G) in the general population?

ERVV-2 p.His48Arg (c.143A>G) is very rare (popmax 0.00549%, eas) (gnomAD).

What do computational predictors say about ERVV-2 p.His48Arg (c.143A>G)?

AlphaMissense predicts likely pathogenic (score 0.5784) — an in-silico prediction, not a clinical call.

ERVV-2 p.His48Arg

c.143A>G · VCV3846190

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.5784 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00549%, eas)

Missense predictors

1/2 damaging

AlphaMissense, SaProt

Computational evidence

Protein change
AlphaMissense	0.5784	likely pathogenic
SaProt	LLR -6.34	tolerated
⇒ AlphaMissense calls this damaging; SaProt does not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.1	GERP 0.18, phastCons 0.017
Regional constraint	o/e 0.31	constrained · MANE · 341 bp · p 8.9e-09 · regional, not allelic
Overall
CADD	15.68	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 0.00549% East Asian · 2/36,434 alleles

Filtering AF 0.000909% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00034%

Overall 0.00185% 15/812,306 alleles · very rare

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0411%	2,431
East Asiangrpmax	0.00549%	18,217
Remaining individualsnot grpmax-eligible	0.00275%	36,376
European (non-Finnish)	0.000726%	137,766

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: ERVV-2
Protein: p.His48Arg
Coding: c.143A>G
MANE Select: NM_001191055
Type: single nucleotide variant
Location: chr19:53049394 (GRCh38)
Gene constraint: LOEUF 1.451 · pLI 0.37 (gnomAD)
Structure: AlphaFold pLDDT 46.18

Full ERVV-2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

ERVV-2 p.Ala337Thr Uncertain significance ★ ⚠ same type
ERVV-2 p.Ala442Ser Uncertain significance ★ ⚠ same type
ERVV-2 p.Ala450Thr Uncertain significance ★ ⚠ same type
ERVV-2 p.Arg195Ser Uncertain significance ★ ⚠ same type
ERVV-2 p.Arg304Gln Uncertain significance ★ ⚠ same type
ERVV-2 p.Arg304Gly Uncertain significance ★ ⚠ same type
ERVV-2 p.Arg441Gly Uncertain significance ★ ⚠ same type
ERVV-2 p.Arg441Lys 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/ervv-2-p-his48arg (accessed [today's date]).

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