Is CCDC77 p.Lys237Arg (c.710A>G) pathogenic?

CCDC77 p.Lys237Arg (c.710A>G) is classified Likely benign in CCDC77 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-06-10). AlphaMissense: likely benign (0.0586); Ultra-rare (popmax 0.0253%, afr).

How common is CCDC77 p.Lys237Arg (c.710A>G) in the general population?

CCDC77 p.Lys237Arg (c.710A>G) is ultra-rare (popmax 0.0253%, afr) (gnomAD).

What do computational predictors say about CCDC77 p.Lys237Arg (c.710A>G)?

AlphaMissense predicts likely benign (score 0.0586) — an in-silico prediction, not a clinical call.

CCDC77 p.Lys237Arg

c.710A>G · VCV3264302

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0586 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0253%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0586	likely benign
REVEL	0.074	moderately benign-leaning
SaProt	LLR -5.73	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 0.41	GERP -3.9, phastCons 0.86
Regional constraint	o/e 0.99	unconstrained · MANE · 33 kb · p 0.78 · regional, not allelic
Overall
CADD	0.127	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 0.0253% African / African-American · 19/75,008 alleles

Filtering AF 0.0165% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.0137%

Overall 0.00452% 73/1,614,102 alleles · ultra-rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.0253%	3,948
Remaining individualsnot grpmax-eligible	0.008%	12,502
European (non-Finnish)	0.00398%	25,106
East Asian	0.00223%	44,882
South Asian	0.0011%	91,080

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: CCDC77
Protein: p.Lys237Arg
Coding: c.710A>G
MANE Select: NM_032358
Type: single nucleotide variant
Location: chr12:433211 (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.Lys237Ile 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-lys237arg (accessed [today's date]).

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