Is SARS1 p.Pro81Ser (c.241C>T) pathogenic?

SARS1 p.Pro81Ser (c.241C>T) is classified Uncertain significance in SARS1 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-06-25). AlphaMissense: likely benign (0.1288); Very rare (popmax 0.00834%, amr).

How common is SARS1 p.Pro81Ser (c.241C>T) in the general population?

SARS1 p.Pro81Ser (c.241C>T) is very rare (popmax 0.00834%, amr) (gnomAD).

What do computational predictors say about SARS1 p.Pro81Ser (c.241C>T)?

AlphaMissense predicts likely benign (score 0.1288) — an in-silico prediction, not a clinical call.

SARS1 p.Pro81Ser

c.241C>T · VCV4159614

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1288 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00834%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1288	likely benign
REVEL	0.358	indeterminate
SaProt	LLR -12.55	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 6	GERP 1.8, phastCons 1
Regional constraint	o/e 0.68	unconstrained · MANE · 23 kb · p 1.2e-13 · regional, not allelic
Overall
CADD	18.99	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 0.00834% Admixed American · 5/59,964 alleles

Filtering AF 0.00323% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00207%

Overall 0.00143% 23/1,613,554 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00834%	11,993
European (non-Finnish)	0.00153%	65,546

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: SARS1
Protein: p.Pro81Ser
Coding: c.241C>T
MANE Select: NM_006513
Type: single nucleotide variant
Location: chr1:109228385 (GRCh38)
Gene constraint: LOEUF 0.57 · pLI 0.41 (gnomAD)
Structure: AlphaFold pLDDT 93.48 · 9 PDB
Residue 81: an α-helix

Full SARS1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

SARS1 p.Pro81Leu Uncertain significance ★ ⚠ same residue
SARS1 p.Arg121Gln Uncertain significance ★★ ⚠ same type
SARS1 p.Arg404Cys Uncertain significance ★★ ⚠ same type
SARS1 c.288+9T>C Benign ★★ same type
SARS1 c.970-22T>C Benign ★★ same type
SARS1 p.Glu149= Benign ★★ same type
SARS1 p.Gly387Glu Benign/Likely benign ★★ ⚠ same type
SARS1 p.Leu297= Likely benign ★★ 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/sars1-p-pro81ser (accessed [today's date]).

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