Is SAG p.Ser371Arg (c.1111A>C) pathogenic?

SAG p.Ser371Arg (c.1111A>C) is classified Uncertain significance in SAG (ClinVar, Single submitter, 1 submitter; last evaluated 2022-07-12). AlphaMissense: likely benign (0.1728); Very rare (popmax 8.48e-05%, nfe).

How common is SAG p.Ser371Arg (c.1111A>C) in the general population?

SAG p.Ser371Arg (c.1111A>C) is very rare (popmax 8.48e-05%, nfe) (gnomAD).

What do computational predictors say about SAG p.Ser371Arg (c.1111A>C)?

AlphaMissense predicts likely benign (score 0.1728) — an in-silico prediction, not a clinical call.

SAG p.Ser371Arg

c.1111A>C · rs1701254072 · VCV1378763

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1728 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 8.48e-05%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1728	likely benign
REVEL	0.059	moderately benign-leaning
SaProt	LLR -7.23	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · A>G here scores Δ0.43 · evaluated, not missing
Constraint at this position
Conservation	phyloP 5	GERP 1.2, phastCons 1
Overall
CADD	18.43	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 8.48e-05% European (non-Finnish) · 1/1,179,762 alleles

Overall 6.2e-05% 1/1,613,716 alleles · very rare exomes 0/1,461,530 · genomes 1/152,186 · joint denominator

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: SAG
Protein: p.Ser371Arg
Coding: c.1111A>C
MANE Select: NM_000541
dbSNP: rs1701254072
Type: single nucleotide variant
Location: chr2:233346411 (GRCh38)
Structure: AlphaFold pLDDT 83.02 · 7 PDB

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

Similar variants

SAG c.1023-2A>G Likely pathogenic ★★ same type
SAG c.1103-2A>C Pathogenic/Likely pathogenic ★★ same type
SAG c.136+2T>C Likely pathogenic ★★ same type
SAG c.136+2T>G Pathogenic/Likely pathogenic ★★ same type
SAG c.181+1G>A Likely pathogenic ★★ same type
SAG c.182-2A>G Pathogenic/Likely pathogenic ★★ same type
SAG c.376-2A>G Pathogenic/Likely pathogenic ★★ same type
SAG c.435+1G>A Likely pathogenic ★★ 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/sag-p-ser371arg (accessed [today's date]).

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