Is CCDC77 p.Arg391Pro (c.1172G>C) pathogenic?

CCDC77 p.Arg391Pro (c.1172G>C) is classified Uncertain significance in CCDC77 (ClinVar, Single submitter, 1 submitter; last evaluated 2021-12-06). AlphaMissense: likely pathogenic (0.962); Absent from gnomAD v4.1.

How common is CCDC77 p.Arg391Pro (c.1172G>C) in the general population?

CCDC77 p.Arg391Pro (c.1172G>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CCDC77 p.Arg391Pro (c.1172G>C)?

AlphaMissense predicts likely pathogenic (score 0.962) — an in-silico prediction, not a clinical call.

CCDC77 p.Arg391Pro

c.1172G>C · rs371461307 · VCV2265053

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely pathogenic

0.962 · ACMG-weighted

gnomAD v4.1

Absent

absent from gnomAD v4.1

Missense predictors

2/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.962	likely pathogenic · top 1% in CCDC77
REVEL	0.603	indeterminate
SaProt	LLR -11.60	damaging
⇒ AlphaMissense and SaProt both call this damaging; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 8.5	GERP 1.9, phastCons 1
Regional constraint	o/e 0.99	unconstrained · MANE · 33 kb · p 0.78 · regional, not allelic
Overall
CADD	28.2	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean damaging — a triage signal, not a reclassification

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: CCDC77
Protein: p.Arg391Pro
Coding: c.1172G>C
MANE Select: NM_032358
dbSNP: rs371461307
Type: single nucleotide variant
Location: chr12:440848 (GRCh38)
Gene constraint: LOEUF 1.077 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.42

Full CCDC77 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC77 p.Arg391Cys Uncertain significance ★ ⚠ same residue
CCDC77 p.Ala157Pro Uncertain significance ★ ⚠ same type
CCDC77 p.Ala194Gly Uncertain significance ★ ⚠ same type
CCDC77 p.Ala445Pro Uncertain significance ★ ⚠ same type
CCDC77 p.Arg134Leu Uncertain significance ★ ⚠ same type
CCDC77 p.Arg216Gly Uncertain significance ★ ⚠ same type
CCDC77 p.Arg251Gln Uncertain significance ★ ⚠ same type
CCDC77 p.Arg251Leu 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/ccdc77-p-arg391pro (accessed [today's date]).

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