Is RET p.Arg312= (c.936G>A) pathogenic?

RET p.Arg312= (c.936G>A) is classified Benign/Likely benign in RET (ClinVar, Multiple submitters, 4 submitters; last evaluated 2025-08-09). Absent from gnomAD v4.1; Associated with hereditary neoplastic syndrome.

What condition is associated with RET p.Arg312= (c.936G>A)?

RET p.Arg312= (c.936G>A) is associated with hereditary neoplastic syndrome, multiple endocrine neoplasia type 2A, multiple endocrine neoplasia type 2 (ClinVar).

How common is RET p.Arg312= (c.936G>A) in the general population?

RET p.Arg312= (c.936G>A) is absent from gnomAD v4.1 (gnomAD).

RET p.Arg312=

c.936G>A · rs1837778702 · VCV1012555

Benign/Likely benign Multiple submitters

Classification

Benign/Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 4 submitters

gnomAD v4.1

Absent

absent from gnomAD v4.1

Conditions

hereditary neoplastic syndrome

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	<0.2	all four deltas below 0.2 · G>T here scores Δ0.76 · evaluated, not missing
Constraint at this position
Conservation	phyloP 0.27	GERP -4, phastCons 0.86
Overall
CADD	5.052	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Absent from gnomAD v4.1. Not observed in any sequenced alleles — a rarity signal (ACMG PM2-supporting), not evidence of pathogenicity on its own.

Variant & gene context

Gene: RET
Protein: p.Arg312=
Coding: c.936G>A
MANE Select: NM_020975
dbSNP: rs1837778702
Type: single nucleotide variant
Location: chr10:43106444 (GRCh38)
Gene constraint: LOEUF 0.24 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 79.27 · 34 PDB
Residue 312: the 'cadherin-like region 3 (cld3)' region

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

Disease context

hereditary neoplastic syndrome — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

Also linked: multiple endocrine neoplasia type 2A multiple endocrine neoplasia type 2

Similar variants

RET p.Arg312Lys Uncertain significance ★ ⚠ same residue
RET p.Arg312fs Pathogenic ★ same residue
RET c.1759+1G>A Pathogenic/Likely pathogenic ★★ same condition
RET c.1879+1G>A Pathogenic/Likely pathogenic ★★ same condition
RET p.Arg180Ter Pathogenic ★★ same condition
RET p.Arg77Cys Pathogenic/Likely pathogenic ★★ ⚠ same condition
RET p.Arg873Trp Likely pathogenic ★★ same condition
RET p.Arg897Ter Pathogenic ★★ same condition

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/ret-p-arg312 (accessed [today's date]).

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