Is CLNK p.Val211Ala (c.632T>C) pathogenic?

CLNK p.Val211Ala (c.632T>C) is classified Uncertain significance in CLNK (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.146); Absent from gnomAD v4.1.

How common is CLNK p.Val211Ala (c.632T>C) in the general population?

CLNK p.Val211Ala (c.632T>C) is absent from gnomAD v4.1 (gnomAD).

What do computational predictors say about CLNK p.Val211Ala (c.632T>C)?

AlphaMissense predicts likely benign (score 0.146) — an in-silico prediction, not a clinical call.

CLNK p.Val211Ala

c.632T>C · VCV4003781

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.146 · ACMG-weighted

gnomAD v4.1

Not reported

no allele count reported in gnomAD v4.1 (AN 1,333,708)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.146	likely benign
REVEL	0.011	strongly benign-leaning
SaProt	LLR -6.46	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	Δ0.26	donor loss, 17 bp away · masked 0 · deltas
Constraint at this position
Conservation	phyloP 3	GERP -1.9, phastCons 1
Regional constraint	o/e 1.07	unconstrained · MANE · 177 kb · p 0.097 · regional, not allelic
Overall
CADD	16.45	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

No allele count reported in gnomAD v4.1 (AN 1,333,708). This is missing data, not an absence: the variant may or may not be present in gnomAD. Rarity (ACMG PM2) and BA1/BS1 cannot be assessed for it.

Variant & gene context

Gene: CLNK
Protein: p.Val211Ala
Coding: c.632T>C
MANE Select: NM_052964
Type: single nucleotide variant
Location: chr4:10528093 (GRCh38)
Gene constraint: LOEUF 1.308 · pLI <0.01 · ClinGen HI 0/3 (gnomAD)
Structure: AlphaFold pLDDT 56.93

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

Similar variants

CLNK p.Val211Ile Uncertain significance ★ ⚠ same residue
CLNK p.Ile361= Benign ★★ same type
CLNK p.Pro31Leu Benign ★★ same type
CLNK p.Ala241Asp Uncertain significance ★ ⚠ same type
CLNK p.Arg184Lys Uncertain significance ★ ⚠ same type
CLNK p.Arg198Ser Uncertain significance ★ ⚠ same type
CLNK p.Arg257Thr Uncertain significance ★ ⚠ same type
CLNK p.Arg298Thr 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/clnk-p-val211ala (accessed [today's date]).

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