Is CCDC157 p.Glu67Lys (c.199G>A) pathogenic?

CCDC157 p.Glu67Lys (c.199G>A) is classified Uncertain significance in CCDC157 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-06-02). AlphaMissense: ambiguous (0.4021); Ultra-rare (popmax 0.0134%, eas).

How common is CCDC157 p.Glu67Lys (c.199G>A) in the general population?

CCDC157 p.Glu67Lys (c.199G>A) is ultra-rare (popmax 0.0134%, eas) (gnomAD).

What do computational predictors say about CCDC157 p.Glu67Lys (c.199G>A)?

AlphaMissense predicts ambiguous (score 0.4021) — an in-silico prediction, not a clinical call.

CCDC157 p.Glu67Lys

c.199G>A · rs766620698 · VCV2556138

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.4021 · ACMG-weighted

gnomAD v4.1

Rare

ultra-rare (popmax 0.0134%, eas)

Computational evidence

Protein change
AlphaMissense	0.4021	ambiguous
REVEL	0.31	indeterminate
SaProt	LLR -10.23	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 9.8	GERP 0.72, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 11 kb · p 0.19 · regional, not allelic
Overall
CADD	28.3	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 0.0134% East Asian · 6/44,874 alleles

Filtering AF 0.00579% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00394%

Overall 0.00103% 15/1,461,404 alleles · ultra-rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.0134%	7,479
Remaining individualsnot grpmax-eligible	0.0016%	62,502
South Asian	0.0011%	91,090
European (non-Finnish)	0.000593%	168,573

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: CCDC157
Protein: p.Glu67Lys
Coding: c.199G>A
MANE Select: NM_001017437
dbSNP: rs766620698
Type: single nucleotide variant
Location: chr22:30366199 (GRCh38)
Gene constraint: LOEUF 1.165 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.73

Full CCDC157 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCDC157 p.Arg45Leu Uncertain significance ★★ ⚠ same type
CCDC157 p.Ala223Pro Uncertain significance ★ ⚠ same type
CCDC157 p.Ala292Val Uncertain significance ★ ⚠ same type
CCDC157 p.Ala300Thr Uncertain significance ★ ⚠ same type
CCDC157 p.Ala317Thr Uncertain significance ★ ⚠ same type
CCDC157 p.Ala324Ser Uncertain significance ★ ⚠ same type
CCDC157 p.Ala32Thr Uncertain significance ★ ⚠ same type
CCDC157 p.Ala389Val 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/ccdc157-p-glu67lys (accessed [today's date]).

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