Is CTHRC1 p.Ser196Pro (c.586T>C) pathogenic?

CTHRC1 p.Ser196Pro (c.586T>C) is classified Uncertain significance in CTHRC1 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-08-26). AlphaMissense: likely pathogenic (0.9421); Absent from gnomAD v4.1.

How common is CTHRC1 p.Ser196Pro (c.586T>C) in the general population?

CTHRC1 p.Ser196Pro (c.586T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CTHRC1 p.Ser196Pro (c.586T>C)?

AlphaMissense predicts likely pathogenic (score 0.9421) — an in-silico prediction, not a clinical call.

CTHRC1 p.Ser196Pro

c.586T>C · VCV3498177

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.9421 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.9421	likely pathogenic
REVEL	0.214	benign-leaning
SaProt	LLR -9.02	tolerated
⇒ AlphaMissense calls this damaging; REVEL and SaProt do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 2.2, phastCons 1
Regional constraint	o/e 0.92	unconstrained · MANE · 11 kb · p 0.18 · regional, not allelic
Overall
CADD	26.8	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

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: CTHRC1
Protein: p.Ser196Pro
Coding: c.586T>C
MANE Select: NM_138455
Type: single nucleotide variant
Location: chr8:103378240 (GRCh38)
Gene constraint: LOEUF 1.127 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.78

Full CTHRC1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CTHRC1 p.Ala124Val Uncertain significance ★ ⚠ same type
CTHRC1 p.Ala174Val Uncertain significance ★ ⚠ same type
CTHRC1 p.Ala40Thr Uncertain significance ★ ⚠ same type
CTHRC1 p.Arg146Gln Uncertain significance ★ ⚠ same type
CTHRC1 p.Arg156Cys Uncertain significance ★ ⚠ same type
CTHRC1 p.Arg193Cys Uncertain significance ★ ⚠ same type
CTHRC1 p.Arg2Gly Uncertain significance ★ ⚠ same type
CTHRC1 p.Arg2Leu 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/cthrc1-p-ser196pro (accessed [today's date]).

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