Is CCRL2 p.Ter345Ser (c.1034A>C) pathogenic?

CCRL2 p.Ter345Ser (c.1034A>C) is classified Benign in CCRL2 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2018-07-23). Rare (popmax 0.912%, afr).

How common is CCRL2 p.Ter345Ser (c.1034A>C) in the general population?

CCRL2 p.Ter345Ser (c.1034A>C) is rare (popmax 0.912%, afr) (gnomAD).

CCRL2 p.Ter345Ser

c.1034A>C · rs137877836 · VCV711365

Benign Multiple submitters

Classification

Benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

Consequence

stop-loss

predicted LoF

gnomAD v4.1

Rare

rare (popmax 0.912%, afr)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Consequence	stop-loss	predicted loss-of-function
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 1.2	GERP -2.9, phastCons 0.01
Overall
CADD	1.1	PHRED · no single calibrated threshold — expert panels disagree

Predicted loss-of-function is descriptive, not an applied PVS1 code.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.912% African / African-American · 680/74,582 alleles

Filtering AF 0.855% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.832%

Overall 0.0456% 729/1,597,866 alleles · rare

Ancestry group	Frequency	1 in
African / African-Americangrpmax	0.912%	110
Middle Eastern	0.0334%	2,997
Admixed American	0.0327%	3,060
Remaining individualsnot grpmax-eligible	0.0323%	3,094
European (non-Finnish)	0.000684%	146,237

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: CCRL2
Protein: p.Ter345Ser
Coding: c.1034A>C
MANE Select: NM_003965
dbSNP: rs137877836
Type: single nucleotide variant
Location: chr3:46409113 (GRCh38)
Gene constraint: LOEUF 1.939 · pLI 0.11 (gnomAD)
Structure: AlphaFold pLDDT 77.93

Full CCRL2 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCRL2 c.-13+173T>A Uncertain significance ★ same type
CCRL2 c.-13+178A>T Uncertain significance ★ same type
CCRL2 c.-13+181C>T Uncertain significance ★ same type
CCRL2 p.Ala252Val Uncertain significance ★ ⚠ same type
CCRL2 p.Ala47Val Uncertain significance ★ ⚠ same type
CCRL2 p.Ala81Thr Uncertain significance ★ ⚠ same type
CCRL2 p.Arg144Lys Uncertain significance ★ ⚠ same type
CCRL2 p.Arg313Cys 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/ccrl2-p-ter345ser (accessed [today's date]).

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