Is CCDC62 p.Val219Ile (c.655G>A) pathogenic?

CCDC62 p.Val219Ile (c.655G>A) is classified Likely benign in CCDC62 (ClinVar, Single submitter, 1 submitter; last evaluated 2025-11-20). AlphaMissense: likely benign (0.082); Very rare (popmax 0.00017%, nfe).

How common is CCDC62 p.Val219Ile (c.655G>A) in the general population?

CCDC62 p.Val219Ile (c.655G>A) is very rare (popmax 0.00017%, nfe) (gnomAD).

What do computational predictors say about CCDC62 p.Val219Ile (c.655G>A)?

AlphaMissense predicts likely benign (score 0.082) — an in-silico prediction, not a clinical call.

CCDC62 p.Val219Ile

c.655G>A · VCV4649588

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.082 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00017%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.082	likely benign
REVEL	0.015	strongly benign-leaning
SaProt	LLR -5.89	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 0.023	GERP -4.2, phastCons 0.26
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 0.00021 · regional, not allelic
Overall
CADD	7.21	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 0.00017% European (non-Finnish) · 2/1,175,166 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000139% 2/1,443,312 alleles · very rare

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: CCDC62
Protein: p.Val219Ile
Coding: c.655G>A
MANE Select: NM_201435
Type: single nucleotide variant
Location: chr12:122788914 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.07
Residue 219: a UniProt-annotated variant site (in spgf67)

Full CCDC62 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC62 p.Gln364= Benign ★★ same type
CCDC62 p.Ala190Gly Uncertain significance ★ ⚠ same type
CCDC62 p.Ala271Glu Uncertain significance ★ ⚠ same type
CCDC62 p.Ala271Ser Uncertain significance ★ ⚠ same type
CCDC62 p.Ala322Asp Uncertain significance ★ ⚠ same type
CCDC62 p.Ala503Gly Uncertain significance ★ ⚠ same type
CCDC62 p.Ala6Ser Uncertain significance ★ ⚠ same type
CCDC62 p.Arg11Cys 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/ccdc62-p-val219ile (accessed [today's date]).

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