Is ATRIP p.Ser31Arg (c.93C>G) pathogenic?

ATRIP p.Ser31Arg (c.93C>G) is classified Uncertain significance in ATRIP (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-02-03). AlphaMissense: ambiguous (0.4475); Very rare (popmax 0.00971%, sas).

How common is ATRIP p.Ser31Arg (c.93C>G) in the general population?

ATRIP p.Ser31Arg (c.93C>G) is very rare (popmax 0.00971%, sas) (gnomAD).

What do computational predictors say about ATRIP p.Ser31Arg (c.93C>G)?

AlphaMissense predicts ambiguous (score 0.4475) — an in-silico prediction, not a clinical call.

ATRIP p.Ser31Arg

c.93C>G · VCV3465348

Uncertain significance Multiple submitters

Classification

Uncertain significance

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

AlphaMissense

ambiguous

0.4475 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00971%, sas)

Missense predictors

0/2 damaging

REVEL, SaProt · AlphaMissense indeterminate

Computational evidence

Protein change
AlphaMissense	0.4475	ambiguous
REVEL	0.051	moderately benign-leaning
SaProt	LLR -6.12	tolerated
⇒ REVEL and SaProt both call this tolerated; AlphaMissense is indeterminate.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · C>T here scores Δ0.23 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.31	GERP -1.8, phastCons 0.91
Regional constraint	o/e 0.95	unconstrained · MANE · 19 kb · p 0.089 · regional, not allelic
Overall
CADD	23.2	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 0.00971% South Asian · 7/72,116 alleles

Filtering AF 0.00452% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00318%

Overall 0.00258% 38/1,472,560 alleles · very rare exomes 32/1,320,286 · genomes 6/152,274 · joint denominator

Ancestry group	Frequency	1 in
Ashkenazi Jewishnot grpmax-eligible	0.0925%	1,081
South Asiangrpmax	0.00971%	10,302
Remaining individualsnot grpmax-eligible	0.00716%	13,962
East Asian	0.00558%	17,918
European (non-Finnish)	0.00018%	556,204

Ashkenazi Jewish shows a higher raw frequency than the grpmax group above it. gnomAD excludes bottlenecked groups — Finnish, Ashkenazi Jewish, Amish and “Remaining individuals” — from grpmax, because founder effects make their frequencies unrepresentative for filtering. The table is sorted by frequency, so an excluded group can sit above the grpmax row.

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: ATRIP
Protein: p.Ser31Arg
Coding: c.93C>G
MANE Select: NM_130384
Type: single nucleotide variant
Location: chr3:48446938 (GRCh38)
Gene constraint: LOEUF 0.707 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 70.10 · 24 PDB
Residue 31: the 'disordered' region

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

Similar variants

TREX1 p.Val31Ile Uncertain significance ★★ ⚠ same residue
ATRIP p.Ser31Asn Uncertain significance ★ ⚠ same residue
ATRIP p.Ser31Ile Uncertain significance ★ ⚠ same residue
ATRIP p.Ser31fs Uncertain significance ★★ same residue
TREX1 p.Arg114His Pathogenic/Likely pathogenic ★★ ⚠ same type
TREX1 p.Arg164Ter Pathogenic/Likely pathogenic ★★ same type
TREX1 p.Asp18Asn Pathogenic ★★ same type
TREX1 p.Asp200His Likely pathogenic ★★ 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/atrip-p-ser31arg (accessed [today's date]).

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