Is SARS2 p.Arg415= (c.1245C>T) pathogenic?

SARS2 p.Arg415= (c.1245C>T) is classified Likely benign in SARS2 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-10-13). Very rare (popmax 0.00466%, nfe).

How common is SARS2 p.Arg415= (c.1245C>T) in the general population?

SARS2 p.Arg415= (c.1245C>T) is very rare (popmax 0.00466%, nfe) (gnomAD).

SARS2 p.Arg415=

c.1245C>T · rs1399849317 · VCV2776556

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

very rare (popmax 0.00466%, nfe)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 4.3	GERP 0.69, phastCons 1
Overall
CADD	7.132	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00466% European (non-Finnish) · 55/1,179,924 alleles

Filtering AF 0.00367% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00329%

Overall 0.00359% 58/1,614,052 alleles · very rare exomes 56/1,461,740 · genomes 2/152,312 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00466%	21,453
Remaining individualsnot grpmax-eligible	0.0032%	31,246
South Asian	0.0011%	91,084

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: SARS2
Protein: p.Arg415=
Coding: c.1245C>T
MANE Select: NM_017827
dbSNP: rs1399849317
Type: single nucleotide variant
Location: chr19:38916230 (GRCh38)
Gene constraint: LOEUF 1.02 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 90.58 · 6 PDB
Residue 415: a β-strand

Full SARS2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SARS2 p.Arg415His Uncertain significance ★★ ⚠ same residue
SARS2 p.Arg415Cys Uncertain significance ★ ⚠ same residue
SARS2 c.759+4T>C Uncertain significance ★★ same type
SARS2 c.-5C>A Uncertain significance ★★ same type
SARS2 p.Ala167Val Uncertain significance ★★ ⚠ same type
SARS2 p.Ala463Val Uncertain significance ★★ ⚠ same type
SARS2 p.Ala516Ser Uncertain significance ★★ ⚠ same type
SARS2 p.Ala73Pro 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/sars2-p-arg415 (accessed [today's date]).

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