Is CCDC62 p.Leu8Phe (c.22C>T) pathogenic?

CCDC62 p.Leu8Phe (c.22C>T) is classified Uncertain significance in CCDC62 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-03-01). AlphaMissense: likely benign (0.0642); Very rare (popmax 0.00847%, nfe).

How common is CCDC62 p.Leu8Phe (c.22C>T) in the general population?

CCDC62 p.Leu8Phe (c.22C>T) is very rare (popmax 0.00847%, nfe) (gnomAD).

What do computational predictors say about CCDC62 p.Leu8Phe (c.22C>T)?

AlphaMissense predicts likely benign (score 0.0642) — an in-silico prediction, not a clinical call.

CCDC62 p.Leu8Phe

c.22C>T · rs1593771046 · VCV3139249

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0642 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00847%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0642	likely benign
REVEL	0.025	moderately benign-leaning
SaProt	LLR -7.48	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 -1.6	GERP -3.5
Regional constraint	o/e 0.87	unconstrained · MANE · 49 kb · p 0.00021 · regional, not allelic
Overall
CADD	0.145	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 0.00847% European (non-Finnish) · 84/991,858 alleles

Filtering AF 0.00699% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00643%

Overall 0.00684% 86/1,256,934 alleles · very rare

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	0.00847%	11,808
East Asian	0.00308%	32,440
Remaining individualsnot grpmax-eligible	0.00216%	46,284

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.Leu8Phe
Coding: c.22C>T
MANE Select: NM_201435
dbSNP: rs1593771046
Type: single nucleotide variant
Location: chr12:122774692 (GRCh38)
Gene constraint: LOEUF 1.012 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 65.07

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-leu8phe (accessed [today's date]).

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