Is CRP p.Ala207Pro (c.619G>C) pathogenic?

CRP p.Ala207Pro (c.619G>C) is classified Uncertain significance in CRP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-16). AlphaMissense: ambiguous (0.4837); Very rare (popmax 0.005%, amr).

How common is CRP p.Ala207Pro (c.619G>C) in the general population?

CRP p.Ala207Pro (c.619G>C) is very rare (popmax 0.005%, amr) (gnomAD).

What do computational predictors say about CRP p.Ala207Pro (c.619G>C)?

AlphaMissense predicts ambiguous (score 0.4837) — an in-silico prediction, not a clinical call.

CRP p.Ala207Pro

c.619G>C · rs769578202 · VCV2403499

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4837 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.005%, amr)

Missense predictors

1/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4837	ambiguous
REVEL	0.132	moderately benign-leaning
SaProt	LLR -12.62	damaging
⇒ SaProt calls this damaging; REVEL does not; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP -10	GERP -3.7
Regional constraint	o/e 1.10	unconstrained · MANE · 957 bp · p 0.11 · regional, not allelic
Overall
CADD	13.83	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 0.005% Admixed American · 3/60,008 alleles

Filtering AF 0.00133% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000668%

Overall 0.000248% 4/1,613,994 alleles · very rare exomes 1/1,461,802 · genomes 3/152,192 · joint denominator

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.005%	20,003
European (non-Finnish)	8.47e-05%	1,180,030

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: CRP
Protein: p.Ala207Pro
Coding: c.619G>C
MANE Select: NM_000567
dbSNP: rs769578202
Type: single nucleotide variant
Location: chr1:159713581 (GRCh38)
Gene constraint: LOEUF 1.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.24 · 24 PDB
Residue 207: the pentraxin (ptx) domain; an α-helix

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

Similar variants

CRP p.Pro43= Benign ★★ same type
CRP p.Thr35= Benign ★★ same type
CRP p.Ala50Gly Uncertain significance ★ ⚠ same type
CRP p.Arg136Lys Uncertain significance ★ ⚠ same type
CRP p.Glu156Lys Uncertain significance ★ ⚠ same type
CRP p.Glu188Asp Uncertain significance ★ ⚠ same type
CRP p.Gly166Arg Uncertain significance ★ ⚠ same type
CRP p.Ile192Met 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/crp-p-ala207pro (accessed [today's date]).

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