Is ANLN p.Val342Phe (c.1024G>T) pathogenic?

ANLN p.Val342Phe (c.1024G>T) is classified Uncertain significance in ANLN (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-12-04). AlphaMissense: likely benign (0.0854); Very rare (popmax 0.004%, afr).

How common is ANLN p.Val342Phe (c.1024G>T) in the general population?

ANLN p.Val342Phe (c.1024G>T) is very rare (popmax 0.004%, afr) (gnomAD).

What do computational predictors say about ANLN p.Val342Phe (c.1024G>T)?

AlphaMissense predicts likely benign (score 0.0854) — an in-silico prediction, not a clinical call.

ANLN p.Val342Phe

c.1024G>T · rs1439550223 · VCV2994483

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

likely benign

0.0854 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.004%, afr)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0854	likely benign
REVEL	0.14	moderately benign-leaning
SaProt	LLR -6.89	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 1.9	GERP 0.46, phastCons 0.25
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.00088 · regional, not allelic
Overall
CADD	12.63	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 0.004% African / African-American · 3/74,916 alleles

Filtering AF 0.00106% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000495%

Overall 0.000186% 3/1,613,750 alleles · very rare

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: ANLN
Protein: p.Val342Phe
Coding: c.1024G>T
MANE Select: NM_018685
dbSNP: rs1439550223
Type: single nucleotide variant
Location: chr7:36407884 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 60.09 · 3 PDB
Residue 342: the 'interaction with f-actin' region

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

Similar variants

ANLN p.Arg431Cys Pathogenic/Likely pathogenic ★★ same type
ANLN c.2653-13G>A Uncertain significance ★★ same type
ANLN p.Ala47Gly Uncertain significance ★★ ⚠ same type
ANLN p.Ala828Thr Uncertain significance ★★ ⚠ same type
ANLN p.Ala940Thr Uncertain significance ★★ ⚠ same type
ANLN p.Arg1040His Uncertain significance ★★ ⚠ same type
ANLN p.Arg154Cys Uncertain significance ★★ ⚠ same type
ANLN p.Arg376Cys 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/anln-p-val342phe (accessed [today's date]).

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