Is COBL p.Ser513Phe (c.1538C>T) pathogenic?

COBL p.Ser513Phe (c.1538C>T) is classified Benign in COBL (ClinVar, Multiple submitters, 3 submitters; last evaluated 2023-12-01). AlphaMissense: likely benign (0.1264); Low-frequency (popmax 1.22%, nfe).

How common is COBL p.Ser513Phe (c.1538C>T) in the general population?

COBL p.Ser513Phe (c.1538C>T) is low-frequency (popmax 1.22%, nfe) (gnomAD).

What do computational predictors say about COBL p.Ser513Phe (c.1538C>T)?

AlphaMissense predicts likely benign (score 0.1264) — an in-silico prediction, not a clinical call.

COBL p.Ser513Phe

c.1538C>T · rs61739178 · VCV774653

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 3 submitters

AlphaMissense

likely benign

0.1264 · ACMG-weighted

gnomAD v4.1

Rare

low-frequency (popmax 1.22%, nfe)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1264	likely benign
REVEL	0.077	moderately benign-leaning
SaProt	LLR -9.82	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 4.2	GERP 1.7, phastCons 1
Regional constraint	o/e 1.02	unconstrained · MANE · 119 kb · p 0.54 · regional, not allelic
Overall
CADD	17.1	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 1.22% European (non-Finnish) · 14,339/1,173,728 alleles

Filtering AF 1.2% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.2%

Overall 1.01% 16,241/1,605,870 alleles · low-frequency exomes 15,063/1,453,586 · genomes 1,178/152,284 · joint denominator

Ancestry group	Frequency	1 in
European (non-Finnish)grpmax	1.22%	82
Admixed American	0.977%	102
Amishnot grpmax-eligible	0.877%	114
Ashkenazi Jewishnot grpmax-eligible	0.865%	116
Remaining individualsnot grpmax-eligible	0.821%	122
Middle Eastern	0.565%	177
Finnishnot grpmax-eligible	0.542%	184
African / African-American	0.162%	619
South Asian	0.0464%	2,157
East Asian	0.00672%	14,873

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: COBL
Protein: p.Ser513Phe
Coding: c.1538C>T
MANE Select: NM_015198
dbSNP: rs61739178
Type: single nucleotide variant
Location: chr7:51029558 (GRCh38)
Gene constraint: LOEUF 0.638 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 50.88 · 1 PDB
Residue 513: the 'disordered' region

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

Similar variants

COBL p.Ala57= Benign ★★ same type
COBL p.Ala655Pro Benign ★★ same type
COBL p.Gly534Ser Likely benign ★★ same type
COBL p.His601Tyr Benign ★★ same type
COBL p.Ser47= Benign ★★ same type
COBL p.Thr1234= Benign ★★ same type
COBL p.Tyr222= Benign ★★ same type
COBL p.Ala1130Ser 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/cobl-p-ser513phe (accessed [today's date]).

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