Is CCDC27 p.Arg572His (c.1715G>A) pathogenic?

CCDC27 p.Arg572His (c.1715G>A) is classified Uncertain significance in CCDC27 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-18). AlphaMissense: likely benign (0.0845); Very rare (popmax 0.00667%, amr).

How common is CCDC27 p.Arg572His (c.1715G>A) in the general population?

CCDC27 p.Arg572His (c.1715G>A) is very rare (popmax 0.00667%, amr) (gnomAD).

What do computational predictors say about CCDC27 p.Arg572His (c.1715G>A)?

AlphaMissense predicts likely benign (score 0.0845) — an in-silico prediction, not a clinical call.

CCDC27 p.Arg572His

c.1715G>A · rs770644260 · VCV3139071

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0845 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00667%, amr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.037	moderately benign-leaning
SaProt	LLR -8.64	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 0.95	GERP -5, phastCons 0.001
Regional constraint	o/e 1.01	unconstrained · MANE · 19 kb · p 0.84 · regional, not allelic
Overall
CADD	11.85	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — 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

Grpmax group 0.00667% Admixed American · 4/59,982 alleles

Filtering AF 0.00226% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00135%

Overall 0.000806% 13/1,613,086 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00667%	14,995
Remaining individualsnot grpmax-eligible	0.0032%	31,231
East Asian	0.00223%	44,888
African / African-American	0.00133%	74,934
European (non-Finnish)	0.000424%	235,995

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: CCDC27
Protein: p.Arg572His
Coding: c.1715G>A
MANE Select: NM_152492
dbSNP: rs770644260
Type: single nucleotide variant
Location: chr1:3767417 (GRCh38)
Gene constraint: LOEUF 1.234 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 66.70

Full CCDC27 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC27 p.Arg572Cys Uncertain significance ★ ⚠ same residue
CCDC27 p.Ala112Pro Uncertain significance ★ ⚠ same type
CCDC27 p.Ala112Val Uncertain significance ★ ⚠ same type
CCDC27 p.Ala153Val Uncertain significance ★ ⚠ same type
CCDC27 p.Ala293Thr Uncertain significance ★ ⚠ same type
CCDC27 p.Ala324Val Uncertain significance ★ ⚠ same type
CCDC27 p.Ala574Val Uncertain significance ★ ⚠ same type
CCDC27 p.Ala78Asp 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/ccdc27-p-arg572his (accessed [today's date]).

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