Is CCL16 p.Val68Ile (c.202G>A) pathogenic?

CCL16 p.Val68Ile (c.202G>A) is classified Likely benign in CCL16 (ClinVar, Single submitter, 1 submitter; last evaluated 2023-12-19). AlphaMissense: likely benign (0.0669); Very rare (popmax 0.0077%, sas).

How common is CCL16 p.Val68Ile (c.202G>A) in the general population?

CCL16 p.Val68Ile (c.202G>A) is very rare (popmax 0.0077%, sas) (gnomAD).

What do computational predictors say about CCL16 p.Val68Ile (c.202G>A)?

AlphaMissense predicts likely benign (score 0.0669) — an in-silico prediction, not a clinical call.

CCL16 p.Val68Ile

c.202G>A · rs752595378 · VCV3139714

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0669 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.0077%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0669	likely benign
REVEL	0.044	moderately benign-leaning
SaProt	LLR -6.17	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 -3	GERP -3.7
Regional constraint	o/e 0.94	unconstrained · MANE · 3,851 bp · p 0.46 · regional, not allelic
Overall
CADD	0.095	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 0.0077% South Asian · 7/90,886 alleles

Filtering AF 0.00359% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00255%

Overall 0.000745% 12/1,611,572 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0077%	12,984
African / African-American	0.00134%	74,828
European (non-Finnish)	0.000339%	294,951

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: CCL16
Protein: p.Val68Ile
Coding: c.202G>A
MANE Select: NM_004590
dbSNP: rs752595378
Type: single nucleotide variant
Location: chr17:35977727 (GRCh38)
Gene constraint: LOEUF 1.676 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 79.62 · 3 PDB
Residue 68: a disulfide bond; a β-strand

Full CCL16 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CCL16 p.Val68Asp Uncertain significance ★ ⚠ same residue
CCL16 p.Ala64Thr Uncertain significance ★ ⚠ same type
CCL16 p.Asp82Asn Uncertain significance ★ ⚠ same type
CCL16 p.Asp82Gly Uncertain significance ★ ⚠ same type
CCL16 p.Glu5Lys Uncertain significance ★ ⚠ same type
CCL16 p.Glu74Ala Uncertain significance ★ ⚠ same type
CCL16 p.Gly112Val Uncertain significance ★ ⚠ same type
CCL16 p.Gly53Glu 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/ccl16-p-val68ile (accessed [today's date]).

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