Is CCDC57 p.Val620Ile (c.1858G>A) pathogenic?

CCDC57 p.Val620Ile (c.1858G>A) is classified Uncertain significance in CCDC57 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-01-23). AlphaMissense: likely benign (0.0845); Rare (popmax 0.114%, nfe).

How common is CCDC57 p.Val620Ile (c.1858G>A) in the general population?

CCDC57 p.Val620Ile (c.1858G>A) is rare (popmax 0.114%, nfe) (gnomAD).

What do computational predictors say about CCDC57 p.Val620Ile (c.1858G>A)?

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

CCDC57 p.Val620Ile

c.1858G>A · rs200938354 · VCV3139209

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

rare (popmax 0.114%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0845	likely benign
REVEL	0.007	strongly benign-leaning
SaProt	LLR -7.31	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 -4.1	GERP -3.2
Overall
CADD	1.199	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 0.114% European (non-Finnish) · 1,345/1,179,076 alleles

Filtering AF 0.109% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.107%

Overall 0.0885% 1,428/1,613,026 alleles · rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.114%	877
Remaining individualsnot grpmax-eligible	0.0416%	2,402
Admixed American	0.035%	2,857
Finnishnot grpmax-eligible	0.0297%	3,368
African / African-American	0.0213%	4,689
East Asian	0.00223%	44,864

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: CCDC57
Protein: p.Val620Ile
Coding: c.1858G>A
MANE Select: NM_001394669
dbSNP: rs200938354
Type: single nucleotide variant
Location: chr17:82171725 (GRCh38)
Gene constraint: LOEUF 1.26 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 71.77
Residue 620: the 'microtubule binding domain' region; the 'disordered' region

Full CCDC57 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC57 p.Ala1009Val Uncertain significance ★ ⚠ same type
CCDC57 p.Ala222Val Uncertain significance ★ ⚠ same type
CCDC57 p.Ala231Val Uncertain significance ★ ⚠ same type
CCDC57 p.Ala329Ser Uncertain significance ★ ⚠ same type
CCDC57 p.Ala469Val Uncertain significance ★ ⚠ same type
CCDC57 p.Ala490Val Uncertain significance ★ ⚠ same type
CCDC57 p.Ala534Thr Uncertain significance ★ ⚠ same type
CCDC57 p.Ala536Pro 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/ccdc57-p-val620ile (accessed [today's date]).

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