Is C1RL p.Ala183Thr (c.547G>A) pathogenic?

C1RL p.Ala183Thr (c.547G>A) is classified Likely benign in C1RL (ClinVar, Single submitter, 1 submitter; last evaluated 2024-11-09). AlphaMissense: likely benign (0.0598); Very rare (popmax 0.00223%, eas).

How common is C1RL p.Ala183Thr (c.547G>A) in the general population?

C1RL p.Ala183Thr (c.547G>A) is very rare (popmax 0.00223%, eas) (gnomAD).

What do computational predictors say about C1RL p.Ala183Thr (c.547G>A)?

AlphaMissense predicts likely benign (score 0.0598) — an in-silico prediction, not a clinical call.

C1RL p.Ala183Thr

c.547G>A · VCV3483470

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0598 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0598	likely benign
REVEL	0.026	moderately benign-leaning
SaProt	LLR -5.99	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 -0.4	GERP -3
Regional constraint	o/e 0.90	unconstrained · MANE · 13 kb · p 0.015 · regional, not allelic
Overall
CADD	1.058	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 0.00223% East Asian · 1/44,872 alleles

Filtering AF 0.000292% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000211%

Overall 0.000616% 9/1,461,714 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,872
European (non-Finnish)	0.000678%	147,496

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: C1RL
Protein: p.Ala183Thr
Coding: c.547G>A
MANE Select: NM_016546
Type: single nucleotide variant
Location: chr12:7099970 (GRCh38)
Gene constraint: LOEUF 1.205 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 77.42
Residue 183: the sushi domain

Full C1RL gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

C1RL p.Ala183Val Uncertain significance ★ ⚠ same residue
C1RL p.Ala202Thr Uncertain significance ★ ⚠ same type
C1RL p.Ala271Asp Uncertain significance ★ ⚠ same type
C1RL p.Ala404Thr Uncertain significance ★ ⚠ same type
C1RL p.Ala45Thr Uncertain significance ★ ⚠ same type
C1RL p.Ala73Pro Uncertain significance ★ ⚠ same type
C1RL p.Ala95Pro Uncertain significance ★ ⚠ same type
C1RL p.Arg136Trp 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/c1rl-p-ala183thr (accessed [today's date]).

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