Is CRP p.Ser14= (c.42T>A) pathogenic?

CRP p.Ser14= (c.42T>A) is classified Likely benign in CRP (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-14). Ultra-rare (popmax 0.0335%, mid).

How common is CRP p.Ser14= (c.42T>A) in the general population?

CRP p.Ser14= (c.42T>A) is ultra-rare (popmax 0.0335%, mid) (gnomAD).

CRP p.Ser14=

c.42T>A · VCV4917568

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

gnomAD v4.1

Rare

ultra-rare (popmax 0.0335%, mid)

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 -0.42	GERP -1.6
Overall
CADD	1.614	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0335% Middle Eastern · 2/5,976 alleles

Filtering AF 0.0059% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00245%

Overall 0.00205% 33/1,613,342 alleles · ultra-rare exomes 31/1,461,702 · genomes 2/151,640 · joint denominator

Ancestry group	Frequency	1 in
Middle Easterngrpmax	0.0335%	2,988
Remaining individualsnot grpmax-eligible	0.0048%	20,824
European (non-Finnish)	0.00237%	42,141

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.Ser14=
Coding: c.42T>A
MANE Select: NM_000567
Type: single nucleotide variant
Location: chr1:159714444 (GRCh38)
Gene constraint: LOEUF 1.932 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 94.24 · 24 PDB

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.Ala207Pro Uncertain significance ★ ⚠ 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

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-ser14 (accessed [today's date]).

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