Is CCDC157 p.Arg691Pro (c.2072G>C) pathogenic?

CCDC157 p.Arg691Pro (c.2072G>C) is classified Uncertain significance in CCDC157 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-04-23). AlphaMissense: likely benign (0.0926); Absent from gnomAD v4.1.

How common is CCDC157 p.Arg691Pro (c.2072G>C) in the general population?

CCDC157 p.Arg691Pro (c.2072G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC157 p.Arg691Pro (c.2072G>C)?

AlphaMissense predicts likely benign (score 0.0926) — an in-silico prediction, not a clinical call.

CCDC157 p.Arg691Pro

c.2072G>C · VCV3263967

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0926 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

1/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0926	likely benign
REVEL	0.01	strongly benign-leaning
SaProt	LLR -12.01	damaging
⇒ SaProt calls this damaging; AlphaMissense and REVEL do not.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.86	GERP -1.6, phastCons 0.005
Regional constraint	o/e 0.96	unconstrained · MANE · 11 kb · p 0.19 · regional, not allelic
Overall
CADD	0.991	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: CCDC157
Protein: p.Arg691Pro
Coding: c.2072G>C
MANE Select: NM_001017437
Type: single nucleotide variant
Location: chr22:30376558 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.73
Residue 691: the 'disordered' region

Full CCDC157 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC157 p.Arg691Gln Uncertain significance ★ ⚠ same residue
CCDC157 p.Arg45Leu Uncertain significance ★★ ⚠ same type
CCDC157 p.Ala223Pro Uncertain significance ★ ⚠ same type
CCDC157 p.Ala292Val Uncertain significance ★ ⚠ same type
CCDC157 p.Ala300Thr Uncertain significance ★ ⚠ same type
CCDC157 p.Ala317Thr Uncertain significance ★ ⚠ same type
CCDC157 p.Ala324Ser Uncertain significance ★ ⚠ same type
CCDC157 p.Ala32Thr 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/ccdc157-p-arg691pro (accessed [today's date]).

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