Is CCDC157 p.Leu486Arg (c.1457T>G) pathogenic?

CCDC157 p.Leu486Arg (c.1457T>G) is classified Uncertain significance in CCDC157 (ClinVar, Single submitter, 1 submitter; last evaluated 2024-05-13). AlphaMissense: likely benign (0.1583); Very rare (popmax 0.00195%, amr).

How common is CCDC157 p.Leu486Arg (c.1457T>G) in the general population?

CCDC157 p.Leu486Arg (c.1457T>G) is very rare (popmax 0.00195%, amr) (gnomAD).

What do computational predictors say about CCDC157 p.Leu486Arg (c.1457T>G)?

AlphaMissense predicts likely benign (score 0.1583) — an in-silico prediction, not a clinical call.

CCDC157 p.Leu486Arg

c.1457T>G · VCV3263969

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1583 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00195%, amr)

Missense predictors

1/2 damaging

AlphaMissense, SaProt · REVEL no call

Computational evidence

Protein change
AlphaMissense	0.1583	likely benign
REVEL	0.341	indeterminate
SaProt	LLR -10.16	damaging
⇒ SaProt calls this damaging; AlphaMissense does not; REVEL makes no call.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 7.9	GERP 1.3, phastCons 1
Regional constraint	o/e 0.96	unconstrained · MANE · 11 kb · p 0.19 · regional, not allelic
Overall
CADD	26.5	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 0.00195% Admixed American · 1/51,334 alleles

Overall 0.00131% 2/152,222 alleles · very rare

Ancestry group	Frequency	1 in
Admixed Americangrpmax	0.00195%	51,334
African / African-American	0.00136%	73,280

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.Leu486Arg
Coding: c.1457T>G
MANE Select: NM_001017437
Type: single nucleotide variant
Location: chr22:30373718 (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-leu486arg (accessed [today's date]).

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