Is CLEC16A p.Asp401Ala (c.1202A>C) pathogenic?

CLEC16A p.Asp401Ala (c.1202A>C) is classified Uncertain significance in CLEC16A (ClinVar, Single submitter, 1 submitter; last evaluated 2024-10-24). AlphaMissense: likely benign (0.1348); Very rare (popmax 0.00879%, sas).

How common is CLEC16A p.Asp401Ala (c.1202A>C) in the general population?

CLEC16A p.Asp401Ala (c.1202A>C) is very rare (popmax 0.00879%, sas) (gnomAD).

What do computational predictors say about CLEC16A p.Asp401Ala (c.1202A>C)?

AlphaMissense predicts likely benign (score 0.1348) — an in-silico prediction, not a clinical call.

CLEC16A p.Asp401Ala

c.1202A>C · VCV3493511

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.1348 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00879%, sas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.1348	likely benign
REVEL	0.164	moderately benign-leaning
SaProt	LLR -6.67	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 11	GERP 2.3, phastCons 1
Regional constraint	o/e 1.05	unconstrained · MANE · 199 kb · p 0.087 · regional, not allelic
Overall
CADD	24.3	PHRED · no single calibrated threshold — expert panels disagree

ClinVar classifies this uncertain; the computational predictors unanimously lean tolerated — a triage signal, not a reclassification

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00879% South Asian · 8/91,042 alleles

Filtering AF 0.00437% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00312%

Overall 0.000753% 11/1,461,446 alleles · very rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.00879%	11,380
European (non-Finnish)	0.000254%	393,278

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: CLEC16A
Protein: p.Asp401Ala
Coding: c.1202A>C
MANE Select: NM_015226
Type: single nucleotide variant
Location: chr16:11003204 (GRCh38)
Gene constraint: LOEUF 0.639 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 72.17
Residue 401: the 'disordered' region

Full CLEC16A gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

CLEC16A p.Glu432= Benign/Likely benign ★★ same type
CLEC16A p.His31= Likely benign ★★ same type
CLEC16A p.Leu948Phe Benign ★★ same type
CLEC16A p.Ser892Asn Likely benign ★★ same type
CLEC16A p.Ser982Asn Likely benign ★★ same type
CLEC16A p.Thr475Met Benign/Likely benign ★★ same type
CLEC16A p.Ala1043Val Uncertain significance ★ ⚠ same type
CLEC16A p.Ala347Thr 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/clec16a-p-asp401ala (accessed [today's date]).

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