Is ATRN p.Pro984Ser (c.2950C>T) pathogenic?

ATRN p.Pro984Ser (c.2950C>T) is classified Uncertain significance in ATRN (ClinVar, Single submitter, 1 submitter; last evaluated 2022-03-24). AlphaMissense: likely benign (0.2153); Very rare (popmax 0.00669%, eas).

How common is ATRN p.Pro984Ser (c.2950C>T) in the general population?

ATRN p.Pro984Ser (c.2950C>T) is very rare (popmax 0.00669%, eas) (gnomAD).

What do computational predictors say about ATRN p.Pro984Ser (c.2950C>T)?

AlphaMissense predicts likely benign (score 0.2153) — an in-silico prediction, not a clinical call.

ATRN p.Pro984Ser

c.2950C>T · rs773681819 · VCV1988607

Uncertain significance Single submitter

Classification

Uncertain significance

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

likely benign

0.2153 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00669%, eas)

Missense predictors

0/3 damaging

AlphaMissense, REVEL, SaProt

Computational evidence

Protein change
AlphaMissense	0.2153	likely benign
REVEL	0.251	benign-leaning
SaProt	LLR -7.06	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 7.7	GERP 1.8, phastCons 1
Regional constraint	o/e 0.64	unconstrained · MANE · 7,850 bp · p 6.6e-11 · regional, not allelic
Overall
CADD	26.0	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 0.00669% East Asian · 3/44,846 alleles

Filtering AF 0.00177% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.000892%

Overall 0.0013% 21/1,612,800 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00669%	14,949
Admixed American	0.00501%	19,969
South Asian	0.0033%	30,305
Remaining individualsnot grpmax-eligible	0.0032%	31,228
African / African-American	0.00267%	37,485
European (non-Finnish)	0.000678%	147,406

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: ATRN
Protein: p.Pro984Ser
Coding: c.2950C>T
MANE Select: NM_139321
dbSNP: rs773681819
Type: single nucleotide variant
Location: chr20:3584083 (GRCh38)
Gene constraint: LOEUF 0.395 · pLI 1.00 (gnomAD)
Structure: AlphaFold pLDDT 79.27

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

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ATRN p.Arg173His Uncertain significance ★★ ⚠ same type
ATRN p.Asn1035Ser Uncertain significance ★★ ⚠ same type
ATRN p.Asn213Ser Uncertain significance ★★ ⚠ same type
ATRN p.Asn300Thr Uncertain significance ★★ ⚠ same type
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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/atrn-p-pro984ser (accessed [today's date]).

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