Is ANLN p.Ser362Pro (c.1084T>C) pathogenic?

ANLN p.Ser362Pro (c.1084T>C) is classified Likely benign in ANLN (ClinVar, Single submitter, 1 submitter; last evaluated 2025-05-19). AlphaMissense: likely benign (0.0715); Rare (popmax 0.181%, eas).

How common is ANLN p.Ser362Pro (c.1084T>C) in the general population?

ANLN p.Ser362Pro (c.1084T>C) is rare (popmax 0.181%, eas) (gnomAD).

What do computational predictors say about ANLN p.Ser362Pro (c.1084T>C)?

AlphaMissense predicts likely benign (score 0.0715) — an in-silico prediction, not a clinical call.

ANLN p.Ser362Pro

c.1084T>C · VCV3918907

Likely benign Single submitter

Classification

Likely benign

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.0715 · ACMG-weighted

gnomAD v4.1

Rare

rare (popmax 0.181%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.0715	likely benign
REVEL	0.036	moderately benign-leaning
SaProt	LLR -5.99	tolerated
⇒ AlphaMissense, REVEL and SaProt all call this tolerated.
Splicing
SpliceAI	<0.2	no splice effect predicted · four deltas, not one · how we know
Constraint at this position
Conservation	phyloP 0.76	GERP 2.2, phastCons 0.91
Regional constraint	o/e 0.90	unconstrained · MANE · 37 kb · p 0.00088 · regional, not allelic
Overall
CADD	14.34	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 0.181% East Asian · 81/44,816 alleles

Filtering AF 0.149% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.137%

Overall 0.00508% 82/1,612,654 alleles · rare exomes 79/1,460,356 · genomes 3/152,298 · joint denominator

Ancestry group	Frequency	1 in
East Asiangrpmax	0.181%	553
Remaining individualsnot grpmax-eligible	0.0016%	62,434

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.Ser362Pro
Coding: c.1084T>C
MANE Select: NM_018685
Type: single nucleotide variant
Location: chr7:36407944 (GRCh38)
Gene constraint: LOEUF 0.537 · pLI 0.08 (gnomAD)
Structure: AlphaFold pLDDT 60.09 · 3 PDB
Residue 362: 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-ser362pro (accessed [today's date]).

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